Transcript lecture18-pulm

Respiratory
Physiology
[the Ins and Outs]
Jim Pierce
Bi 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?
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Ventilation Perfusion
Matching
Shunt
Shunt
Ventilation Perfusion
Matching
• How do we match ventilation and
perfusion?
Ventilation Perfusion
Matching
• When a lung is not ventilated,
the pAO2 falls
• Then, the vasculature constricts
• Then, the perfusion decreases
Ventilation Perfusion
Matching
• When a lung is not perfused, the pACO2
falls
• This causes bronchoconstriction
• This leads to decreased ventilation.
Ventilation Perfusion
Matching
• Thus, VQ matching is based on:
• Airways and the vessels sending
air and blood away
from mismatched areas.
Ventilation Perfusion
Matching
• 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
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 Pierce
Bi 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
Chronic
Bronchitis
COPD
• Clinical Diagnosis
– History
– Physical
• Physiologic Diagnosis
– Physiologic Testing
• Pathologic Diagnosis
– Anatomic Changes
– Pathologic (Histology) Changes
COPD
Asthma
Emphysema
Physiologic Diagnosis
Chronic
Bronchitis
Clinical Diagnosis
Pathologic
Diagnosis
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
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 Exhale
necessary just to allow inhalation
– Dimensions Make Muscles function
Suboptimally 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 obstruction
causes air trapping
• Air trapping causes
Airways to stay open
COPD
Asthma
Emphysema
Physiologic Diagnosis
Chronic
Bronchitis
Clinical Diagnosis
Pathologic
Diagnosis
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 Physiology
on Pulmonary Function Tests
• Gets better with Smooth Muscle
Relaxant (beta-adrenergic agonist)
Asthma
Emphysema
• Pathologic Diagnosis
• A Biopsy (or Autopsy)
demonstrates destruction of
alveoli and airway walls
leading to decreased elasticity
Normal Lung versus
Emphysema
Normal Lung versus
Emphysema
COPD
• USA:
• 14.2 Million People have COPD
– 12.5 Million
– 1.7 Million
Chronic Bronchitis
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/moderate
stage 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 with
Acute Exacerbations
• Leads to some combination:
– Secretions (Clinical)
– Airway Reactivity (Physiologic)
– Parenchymal Destruction (Pathologic)
Diagnosis
• Threshold of Diagnosis
MUST be related to therapy
• Examples:
– Smoking Cessation
– Surgery
Diagnosis
•
•
•
•
•
History
Physical
Chest XRay / CT scan
Arterial Blood Gas
Pulmonary Function Tests
• Autopsy
CXR
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 course
of lung mechanical physiotherapy
• Exercise Protocol and Classes
• Oxygen and Medication Adjustment
• Perioperative Teaching
– Randomized to Bilateral LVRS
versus 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 management
by 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 via
Level One evidence
– Subset of Patients benefiting from surgery
– Subset of Patients harmed by surgery
– Efficacy of Medical Therapy
Thanks!