Respiratory Physiology [the Ins and Outs] Jim Pierce Bi 145a Lecture 18, 2009-10.

Respiratory Physiology[the Ins and Outs]

Jim PierceBi 145a

Lecture 18, 2009-10

Pulmonary Blood Flow

Pulmonary Ventilation

Pulmonary Ventilation

Compare and Contrast

Ventilation and Perfusion

Ventilation Perfusion Matching

• We have seen that proper gas exchange depends on both ventilation and perfusion

• How do we make sure that each lung unit is both ventilated and perfused?


• How do we match ventilation and perfusion?


• When a lung is not ventilated, the pAO2 falls

• Then, the vasculature constricts

• Then, the perfusion decreases


• When a lung is not perfused, the pACO2 falls

• This causes bronchoconstriction

• This leads to decreased ventilation.


• Thus, VQ matching is based on:

• Airways and the vessels sending air and blood away from mismatched areas.


• This is a great system to compensate for a focal problem (like pneumonia)

• It can be dangerous, however…

Ventilation Perfusion matching

• If there is a global problem with ventilation or perfusion, the whole lung tries to send air or blood elsewhere.

• This is a problem.

• ARDS

Pulmonary Function

• How do we adjust pulmonary function to compensate for changes in the periphery?

Pulmonary Function

• Ultimately, the job of the cardiopulmonary system is to deliver oxygen to the periphery

• As oxygen is used by the periphery, carbon dioxide is returned.

Pulmonary Function

• The cardiovascular system is responsible for delivering the oxygen to the periphery.

• The periphery is responsible for extracting oxygen from the blood

• The venous blood carries the resulting carbon dioxide back to the lung

• The pulmonary system, then, needs to compensate to excrete that carbon dioxide.

CardioPulmonary Control

Pulmonary Function

• How do we increase the delivery of oxygen to the periphery?

• DO2 = CartO2 * CO

• CO = HR * SV

• CO = BP / SVR

Pulmonary Function

• Why doesn’t an increase in the CO cause a decrease in the oxygenation of the blood?

Pulmonary Function

Pulmonary Function

• Answer:

• Built-in Reserve

Pulmonary Function

• What kinds of Carbon Dioxide stresses do we need to deal with?

• Increased / Decreased production of CO2

• pH abnormalities affecting CO2 excretion

Pulmonary Function

• There are two types of protons carried in the blood

• “Volatile acids” that result from CO2 conversion to bicarbonate and protons

• “Non-volatile acids” that result from proton dissociation from other molecules (lactic acid, protein metabolism)

Respiratory Acid-Base Balance

Pulmonary Function

• To increase the disposal of CO2 and remove volatile protons, we simply increase alveolar ventilation

• Minute Ventilation =

Respiratory Rate * Tidal Volume

Pulmonary Function

• Increased production of CO2 and volatile acid occurs primarily because of a change in metabolic substrates to fats

Pulmonary Function

• What about pH problems not related to carbon dioxide?

• They can occur by two mechanisms

• 1) the wrong number of protons

• 2) the wrong amount of buffer

Pulmonary Function

• The wrong number of protons can happen for a variety of reasons:

– Too many made (lactic acid, protein metabolism)

– Too many lost (vomiting stomach acid, renal losses)

– Not enough lost (renal failure)

Pulmonary Function

• The wrong amount of buffer can happen for two reasons:

– Too much buffer (ingestion of alkali, infusion of buffer)

– Too little buffer (loss of buffer with diarrhea, loss of buffer through kidney)

Pulmonary Function

• Since pH changes can affect cellular respiration and CO2 excretion, the lung must be able to compensate for pH changes.

• Ventilation changes cause pCO2 changes

• pCO2 changes cause pH changes

Pulmonary Function

• A high pH is called an alkalemia

• A low pH is called an acidemia

• A particular derangement that causes an increase in pH is called an alkalosis

• A particular derangement that causes a decrease in pH is called an acidosis.

Pulmonary Function

• If an acidosis or alkalosis is caused by changes in ventilation, it is called a Respiratory acidosis/alkalosis

• If is not caused by ventilation, then it is called a Metabolic acidosis/alkalosis

Respiratory Acid-Base Balance

Pulmonary Function

• As we will see in acid-base physiology, the lung compensates for pH changes by changing ventilation and therefore changing pCO2

Questions?

Mechanical Ventilation

Jim PierceBi 145a

Bonus Lecture

Mechanical Ventilation

Mechanical Ventilation• ... is a therapy.

• What are the indications?

• What is the end point?

• How do we administer it?

• How do we assess it?

Lung Functions

• Oxygenation

• Ventilation

• Neurohormonal

Indications for Mechanical Ventilation• Acute Respiratory Failure (66%)

– Acute Respiratory Distress Syndrome – Heart Failure (through pulmonary edema/hypertension)– Pneumonia– Sepsis– Complications of Surgery– Trauma

• Coma (15%)• Acute Exacerbation of Chronic Obstructive

Pulmonary Dz (13%)• Neuromuscular Disease (5%)

Esteban A, Anzueto A, Alia I, et al. How is mechanical ventilation employed in the intensive care unit? An international utilitzation review. American Journal of Respiratory Critical Care Medicine 2000; 161: 1450-1458

Discontinuing Mechanical Ventilation

• Death• Weaning

– Up to 25% of patients have respiratory distress severe enough to require reinstitution of ventilator.

• Extubation– 10 - 20 % of extubated patients who were

successfully weaned require reintubation.

Brochard L, Rauss A, Benito S, et al. Comparison of three methods of gradual withdrawing from ventilatory support during weaning from mechanical ventilation. American Journal of Respiratory Critical Care Medicine. 1994; 150: 896-903.

Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. New England Journal of Medicine. 1995; 332: 345-350.

CMV – Continuous Manditory Ventilation

• The Original Mechanical Vent– Understanding CMV is Vents 101

• Replaced the “medical student”

• Has since been replaced in most locations in the hospital by fancier settings

• Still used in the Operating Room

CMV• Three Variables

– 1) Respiratory Rate– 2) Tidal Volume

– 3) FIO2

CMV• The Tidal Volume with the set FIO2 gets

blown into the patient at the set respiratory rate.

• This is Positive Pressure Ventilation!– (“regular” breathing is negative pressure

ventilation)

Airway Pressure

• If we measure the pressure in the tubing at the end of expiration, it will be barometric pressure. (To make it easier, we call it “zero”)

• Inhalation generates a negative pressure so that air will flow from “zero” to “negative”

• Machines generate a postitive pressure so that air will flow from “positive” to “zero”

CMV• CMV – RR / Vt / FIO2

– CMV 12 / 600 / 30%

• Minute Ventilation = Respiratory Rate * Tidal Volume– 12 / min * 600 cc = 7.2 L/min

• pAo2 = FIO2 * (760 – 47)– 30% * 713 = 213.9 mmHg O2

Assessment of Mechanical Ventilation

Arterial Blood Gas

pH / pCO2 / pO2 / Bicarb / BE / Sat%

7.40 / 40 / 90 / 24 / 0.0 / 99%

Pulse Ox

Driving Mechanical Ventilation

• Our Primary Concern is CO2

– Increase Ventilation by:• Increasing RR or Increasing Vt

– Decrease Ventilation by:• Decreasing RR or Decreasing Vt

• Our Secondary Concern is O2

– We will talk more about O2 in a moment

Driving CMV• Assess pCO2

– If pCO2 is high, we are hypoventilating

– Increase minute ventilation

– If pCO2 is low, we are hyperventilating

– Decrease minute ventilation

Driving CMV• Assess pO2

– If paO2 is normal or high, then the patient is oxygenating well.

– Turn down FIO2 to minimize oxygen toxicity and remove unnecessary other therapies.

Driving CMV• Assess pO2

– If paO2 is low, then the patient is oxygentating poorly.

– Turn up the FIO2 and institute other therapies to improve oxygenation.

CMV• Advantages

– Easy to set up: need a bellows, a motor, and a timer.

– Easy to adjust the settings

• Main Disadvantage– If the Patient is breathing spontaneously, the

patient will be fighting the ventilator.

Ventilators 201• CMV has its major limitation

• New, fancier machines were invented to try to coordinate a patient’s spontaneous breathing with ventilator support.

Assist – Control (AC)• If a patient is spontaneously breathing, the

patient will be assisted.

• If the patient fails to spontaneously breath, then the patient will be on Controlled Manditory Ventilation.

Assist - Control• How do we know if a patient is

spontaneously breathing?

• At end expiration, the pressure at the mouth is “zero.”

• If the patient tries to inhale, the pressure at the mouth is “negative.”

Assist - Control• What kind of assistance does a patient

need?

• The patient is spontaneously breathing so we are assisting his VENTILATION.– Respiratory Rate– Tidal Volume

Assist Control Settings• AC RR / Vt / FIO2

• Respiratory Rate– If the patient does not breath every 60 / RR seconds,

the patient gets a controlled ventilation.– If the patient initiates a negative pressure before 60 /

RR seconds, the patient gets a controlled ventilation.

Assist Control Settings

• Every Single Breath, whether assisted or controlled gets the full Tidal Volume.

Assist Control• Advantages

– allows spontaneous breathing– supports each tidal volume

• Disadvantages– gives a full tidal volume for each spontaneous breath– patient can overbreathe and hyperventilate

IMV - Intermittent Manditory Ventilation• The IMV setting is designed to assist the

patient in obtaining a minimum minute ventilation.

• If the patient tries to overbreathe, then the ventilator does not assist the patient.

IMV – Intermittent Manditory Ventilation• Originally, IMV was CMV

– The patient received CMV RR / Vt / FIO2

– The patient could attempt to spontaneously breathe against the resistance of the tubing (with or without success)

IMV – Intermittent Manditory Ventilation• Then, IMV was CMV with Pressure

Support

– The patient received CMV RR / Vt / FIO2

– If the patient attempted to spontaneously breathe, the patient would receive Pressure Support

Pressure Support

• Inspiratory Flow is proportional to the pressure gradient and inversely proportional to the resistance between the outside world and the lungs

• The ET tube and Vent Circuit generate a fixed resistance.

Pressure Support

• To overcome that increased resistance, the pressure gradient must increase.

• Either the patient must generate more negative pressures (very tiring) or the patient must be provided with more positive pressure from the ventilatory circuit.

Pressure Support

• This increased pressure from the ventilator circuit must be provided only during inspiration

• Thus, Pressure Support is triggered by spontaneous breath, and blows into the tubing at a fixed pressure until inspiration ends.– (Often when inspiratory flow drops)

SIMV – Synchronized Intermittent Manditory Ventilation

• IMV (CMV with PS) still had the disadvantage of not coordinating spontaneous breaths with mandatory breaths.

• Thus, SIMV was invented.

SIMV

• When the patient spontaneously breathes, there is pressure support.

• Intermittently, the ventilator “manditorily” ventilates to insure a minimum minute ventilation.

• These Intermittent Manditory Ventilations are synchronized to only occur on spontaneous breaths.

SIMV Synchronization

• Begin with a spontaneously triggered manditory ventilation

• The patient has 60 / RR seconds to spontaneously breath with PS

• At 60 / RR seconds, the next spontaneous breath receives a manditory full ventilation

• If there is no spontaneous breath, then a controlled manditory ventilation is delivered.

SIMV Assessment• Settings

– SIMV RR / Vt / FIO2 with PS– SIMV 8 / 700 / 30% with PS 12

• Assess– Settings / Arterial Blood Gas– Actual Respiratory Rate– Measured Minute Ventilation– Spontaneous Tidal Volume

SIMV Assessment

• Measured Minute Ventilation = IMV Minute Ventilation +

PS Minute Ventilation– IMV M.V. = RR * Vt

– PS M.V. = Total M.V – IMV M.V.– Average Spontaneous Tidal Vol = PS M.V /

(RRactual – RRset)

Oxygenation• What is the number one cause of V-Q

Mismatch?

• Atelectasis

Oxygenation• How do we fix V-Q mismatch caused by

atelectasis?

• Recruit the unused alveoli to increase “V”

Oxygenation• How do we recruit alveoli?• PEEP

– Positive end expiratory pressure– Decreases the expiratory gradient– Causes air trapping– Trapped air tries to distribute evenly and leads to

opening of all airways.

Oxygenation• What about decreasing the expiratory time

relative to the inspiratory time?

• This leads to air trapping. Since it behaves like peep, we call it:

AUTO-PEEP

Oxygenation• All patients on a ventilator have some amount of

atelectasis

• When a patient is oxygenating poorly, we can try to improve VQ matching by fixing that atelectasis with PEEP or AUTO-PEEP

Questions?

COPD

(Bonus Lecture)Jim Pierce

COPD

• Chronic Obstructive Pulmonary Disease

• A group of diseases

• Intrathoracic Obstruction

COPD

Asthma Emphysema

ChronicBronchitis

COPD• Clinical Diagnosis

– History– Physical

• Physiologic Diagnosis– Physiologic Testing

• Pathologic Diagnosis– Anatomic Changes– Pathologic (Histology) Changes

COPD

Asthma Emphysema

ChronicBronchitis

Clinical Diagnosis

Physiologic Diagnosis

PathologicDiagnosis

COPD

• Why are they grouped together?

• Intrathoracic Obstruction

COPD

• Intrathoracic Obstruction:

• Inspiration– Transthoracic Pressure Gradient– Airways Pulled Open

• Expiration– Recoil or Transthoracic Gradient– Airways Pushed Closed

COPD

• Inspiration

• Relatively Normal Mechanics

• Expiration

• Abnormal Mechanics(Prolonged Expiratory Time)

Hysteresis

COPD

• Early:– Enough Expiratory Reserve

• Middle:– Expiratory Reserve Depleted– Air Trapping– Shift of Hysteresis Curve

COPD

• Late:– Expiratory Reserve Depleted– Air Trapping causes Inefficiency– Inefficiency so severe Active Exhale

necessary just to allow inhalation

– Increase in Work of Breathing

COPD

• Very Late:– Air Trapping causes Inefficiency– Air Trapping changes Diaphragm

and Chest Dimensions

– Inefficiency so severe Active Exhalenecessary just to allow inhalation

– Dimensions Make Muscles functionSuboptimally Due to Angle and Length

COPD

• Classic Description:

• Barrel Chest

• Pursed Lip Breathing

• Shortness of Breath

Barrel Chest

Pursed Lip Breathing

COPD

• Why does pursed lip breathing work?

• Fixed airway obstructioncauses air trapping

• Air trapping causesAirways to stay open

COPD

Asthma Emphysema

ChronicBronchitis

Clinical Diagnosis

Physiologic Diagnosis

PathologicDiagnosis

Chronic Bronchitis

• Clinical Diagnosis

• History:– Cough that leads to Sputum– Almost Daily– At least 3 months of year– At least 2 years

Asthma

• Physiologic Diagnosis

• Obstructive Physiologyon Pulmonary Function Tests

• Gets better with Smooth MuscleRelaxant (beta-adrenergic agonist)

Asthma

Emphysema

• Pathologic Diagnosis

• A Biopsy (or Autopsy)demonstrates destruction of alveoli and airway wallsleading to decreased elasticity

Normal Lung versus Emphysema

COPD

• USA:

• 14.2 Million People have COPD– 12.5 Million Chronic Bronchitis– 1.7 Million Emphysema

• Globally:

• 9-10% of people 40 and older

COPD

• Yearly Mortality, USA:

• Males 50-80: 200 per 100,000

• Females 50-80: 80 per 100,000

COPD

• The Truth:

• No one has just “one” disease.

• There are components of– Sputum Production and SOB– Physiologic reversible obstruction– Destruction of Lung Parenchyma

COPD• History:

• Generally starts 40-50 yrs• More frequently male• Chronic Cough, worse in morning• Sputum Clear or Carbonaceous• 20 cigarettes a day for 20 years• Shortness of breath, esp. on exertion

COPD

• History:

• Initially presents with either cough or acute illness (bronchitis/pneumonia)

• Over years, more frequent acute exacerbations / attacks

• By 60’s, usually breathless on minimal exertion

COPD• Physical Exam

• Not very good at mild/moderatestage of illness

• VERY sensitive for severe illness– Barrel Chest– Weight loss– Coughing– Pursed Lip Breathing

COPD

• Causes:

• Smoking

• Air Pollution

• Airway Hyper-responsiveness

• Alpha1-Anti-Trypsin Deficiency

Pathogenesis• Inflammation

• Case 1:– Stimulus leads to local inflammatory

mediators in airway– Smooth Muscle responds to cytokines by

increase in tone and reactivity– This leads to chronic secretion stasis– This leads to frequent acute attacks

Pathogenesis

• Inflammation

• Case 2:– Stimulus leads to local inflammatory

mediators in airway– Smooth Muscle responds by hypertrophy and

Connective tissue responds by Scar– This leads to chronic secretion stasis– This leads to frequent acute attacks

Pathogenesis

• Inflammation

• Case 3:– Inflammatory mediators lead to mucus gland

hypertrophy and increase in sputum– This leads to sputum trapping and stasis,

leading to more acute exacerbations

Pathogenesis

• Inflammation

• Case 4:– Inflammatory mediators lead to an imbalance

of proteinases (specifically MMP/TIMP imbalance)

– This leads to destruction of airway walls and pathophysiology of COPD

Pathogenesis

• In all cases:

• Chronic Inflammation withAcute Exacerbations

• Leads to some combination:– Secretions (Clinical)– Airway Reactivity (Physiologic)– Parenchymal Destruction (Pathologic)

Diagnosis

• Threshold of DiagnosisMUST be related to therapy

• Examples:– Smoking Cessation– Surgery

Diagnosis

• History

• Physical

• Chest XRay / CT scan

• Arterial Blood Gas

• Pulmonary Function Tests

• Autopsy

CT Scan

Pulmonary Function Tests

Therapy

• Smoking Cessation

• Pulmonary Rehabilitation

• Medication

• Surgery

Therapy• Oxygen• Bronchodilators (Beta-Agonist)• Anticholinergic• Anti-inflammatory

– Topical Steriod– Oral/IV Steroid– Anti-Leukotrienes

• Mucolytic• Anti-Allergy• Antibiotics

Surgery

• Lung Volume Reduction Surgery

• NETT Trial

NETT

• National Emphysema Treatment Trial

– 1996: Participating Centers announced– 1997: Screening for entry begins– July 2002: Recruitment Ends

NETT• After recruitment, patients:

– Underwent exercise testing, pulmonary function testing, and radiography.

– Met with a Pulmonologist, Cardiologist, and Thoracic Surgeon

– Completed a 6-10 week courseof lung mechanical physiotherapy

• Exercise Protocol and Classes

• Oxygen and Medication Adjustment

• Perioperative Teaching

– Randomized to Bilateral LVRSversus continuing physiotherapy

NETT

• Inclusion Criteria– Diagnosis of Emphysema– Met Radiologic and PFT criteria– Accepted by all Physicians– “Severe Impact on Function”

NETT

• Exclusion Criteria– Active smoker (within 4 months)– Unstable angina or cardiac arrhythmia– Heart attack within 6 months– Had certain thoracic or cardiac surgeries or

had another disease that was likely to interfere with participation in the trial or to reduce survival.

NETT

• Medical Arm– Continued Physiotherapy and

Oxygen/Medication managementby Center Pulmonologists

• Surgical Arm– Bilateral LVRS– Open (median sternotomy)

and Thoracoscopic both allowed

NETT

• 3777 people evaluated

• 1218 individuals selected

• 608 assigned surgery

• 610 assigned medical therapy only

• 95% received treatment as directed

• 99% surviving participants followup

NETT

• Interim Outcomes– May 2001 – – Homogenous Disease identified

as having less post operative benefit– Severe Emphysema with Homogenous

Disease noted to have increased risk of death– Interim results published in NEJM– Inclusion criteria adjusted

NETT

• Final Outcomes

– Overall Long-term Mortality identical between Surgical and Medical arms

• 3 month Mortality 7.9% in surgery arm• 3 month Mortality 1.3% in medical arm

NETT• Mostly upper-lobe emphysema:

– With low exercise capacity• More likely to live longer after LVRS• More likely to function better after LVRS than after

medical treatment

– With high exercise capacity • No difference in survival between the LVRS and

Medical participants• Surgical group more likely to function better than

medical group

NETT

• Mostly non upper-lobe emphysema:– With low exercise capacity

• Similar survival and exercise ability after LVRS as after medical treatment

• Had less shortness of breath.

– With high exercise capacity • Had poorer survival after LVRS than after medical

treatment• Both LVRS and Medical participants had similar

low chance of functioning better

NETT

• Identified and supported viaLevel One evidence

– Subset of Patients benefiting from surgery– Subset of Patients harmed by surgery

– Efficacy of Medical Therapy

Thanks!

Respiratory Physiology [the Ins and Outs] Jim Pierce Bi 145a Lecture 18, 2009-10.

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Transcript of Respiratory Physiology [the Ins and Outs] Jim Pierce Bi 145a Lecture 18, 2009-10.