“All I Need is the Air That I Breathe”
Review of Pulmonary Anatomy and Physiology
Eric Olson, MD
Associate Professor of Medicine
College of Medicine
Mayo Clinic
2016 Big Sky Pulmonary Conference
©2015 MFMER | slide-1
Disclosures
• None
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Atmosphere
Lungs
Heart
O2
CO2
Mitochondria
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Overview:
Anatomy
250 million L of air
partake in
respiration
over a lifetime!
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Upper Airway Anatomy
* Tonsil locations
Hard palate
*
Epiglottis
**
Vocal fold
Nasopharynx
Velopharynx
Oropharynx
Hypopharynx
Esophagus
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Nostril (nares)
Nasal ala
Columella
Bone
(tan)
Cartilage
(gray)
https://www.clinicalkey.com/
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Nasal polyps
Sinusitis
https://www.clinicalkey.com/
Septal
deviation
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Grading of Tongue-Palate Relationship,
Palatine Tonsil Size
Friedman M. Otolayngol Head Neck Surg 2002; 127:13
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https://www.clinicalkey.com/
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Stridor: Sign of Vocal Cord Dysfunction
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Airway Tree: 23 Generations
bronchi
bronchiole
Conducting airways
•
•
bronchi
terminal bronchiole
lead air to the site of exchange
Respiratory airways
•
•
respiratory bronchiole
alveoli
site of gas exchange
https://www.clinicalkey.com/
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Lining of Conducting Airways
goblet cells
cilia
Microscopic view
Cilia beat in coordinated fashion causing
mouthward movement of mucous and
trapped inhaled particles
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Asthma: Airway Wall Findings
Normal Bronchiole
Bronchiolar
Smooth Muscle Thickening
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Asthma: Airway Wall Findings (cont)
Goblet Cell Hyperplasia
Thickened Basement Membrane
Eosinophils
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Bronchiectasis
Airway
Pulmonary
Artery
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Bronchiectasis
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Terminal bronchiole
Respiratory bronchioles
Pulmonary
acinus
Alveoli
https://www.clinicalkey.com/
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Centrilobular (smoking-related) Emphysema
AS+AS
RB3
Septum
RB3
RB3
RB2
RB1
TB
RB3
Inflamed
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Pulmonary Lobule; Contain 3-6 acini
Acinus: Lung derived from a terminal bronchiole
Pulmonary
artery
Terminal
bronchioles
Interlobular
septa
Lymphatics; veins
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Clinical Application:
Causes of Interlobular Septal Thickening
Normal
Congestive
heart failure
(smooth septal
thickening)
Lymphangitic
spread of
malignancy
(beaded septal
thickening)
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Alveolar-Capillary Interface
pneumocytes
capillary
alveolus
Microscopic view
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Alveolar-Capillary Interface
Surfactant
Alveolar
macrophage
capillary
lumen
Type II
pneumocyte
Alveolus
Interstitium
Type I
pneumocyte
capillary
lumen
Schematic view
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ARDS
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2 Blood Supplies: Bronchial and Pulmonary
Airway
bleeding
source
Alveolar
bleeding
source
Aird WC. Circ Res 2007;100:174
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Special Properties of Pulmonary Circulation:
Hypoxic Vasoconstriction; Recruitment
Hypoxic
vasoconstriction
Recruitment
Clinical Respiratory Medicine, 4th ed. Spiro SG, Silvestri GA, Agusti A, eds. Elsevier, 2012
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Pulmonary Lymphatic System
https://www.studyblue.com/notes/note/n/gi-and-metabolism-anatomy/deck/10205673
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Thoracic Lung Node Stations
Clinical
application:
Lymph node
involvement
important
determinant
in lung cancer
treatment
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Interim Summary
• Air travels 23 airway generations
• Examples of airways disease
• Larynx: stridor
• Conducting bronchi: asthma, bronchiectasis
• Bronchioles: COPD
• Site of gas exchange: alveolus
• Impressive area for gas exchange
• 2 arterial supplies to the lung
• Bronchial: airways
• Pulmonary: alveoli; capable of hypoxic
vasoconstriction, recruitment during exercise
• Lymphatics: filtering system
• Critical in lung cancer staging
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Overview: Physiology
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Central
Control
O2, CO2
Exchange
Ventilation
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Central Respiratory Control
VRG (I, E)
Central
Pacemaker
DRG (I)
Pontine
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“Wakefulness drive to breathe”
+
Clinical Respiratory Medicine, 4th ed. Spiro SG, Silvestri GA, Agusti A, eds. Elsevier, 2012
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Response to CO2
• Ventilation  2 to 3 L/min for
every 1mmHg  PCO2
Ventilation (L/min)
PAO2 55
PAO2 100
• Lower the PO2, the brisker the
response
• With chronic hypercapnia,
ventilatory drive arising from
central chemosensors will be
lower
30
40
50
60
PACO2
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Response to O2
Ventilation (L/min)
• Markedly increases when
PAO2 < 50-60
PACO2 50
• Response to hypoxia
augmented by  PACO2
PACO2 40
40
50
60
70
80
90
PAO2
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Sleep: Loss of Wakefulness Drive
Central
Pacemaker
Sleep
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Physiologic Changes in Breathing During Sleep
• Controller of ventilation: CO2
• Respiratory rate: ↔
• Tidal volume: ↓
• Upper airway muscles: ↓
• Ventilation: ↓ (10-15%)
• PCO2: ↑ (3-7 mm Hg)
• SpO2: ↓ (1-3%)
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Physiologic Changes in Breathing:
NREM vs REM
NREM
REM
Tidal volume
Regular
Irregular
Resp rate
Regular
Irregular
CO2
responsiveness
O2
responsiveness
Accessory
muscles
↔ or ↓
↓
↔ or ↓
↓
Normal
Paralyzed
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Upper Airway Muscles and Sleep
Tensor palatini
Awake
(stiffens palate)
NREM
Tensor
Palatini EMG
↓ Tonic activity
Genioglossus
(protrudes tongue)
↓ Negative pressure reflex
Changes in upper airway during sleep leaves an
anatomically challenged pharynx vulnerable to collapse
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Clinical Application:
Loss of Accessory Muscle Input in Stage R
results in deeper desaturations in COPD, ALS
REM
REM
REM
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Sleep and Asthma
• Circadian drop in airway caliber at night
• More dramatic in asthmatics
• More deaths from asthma per hour at night than by
day
• Nocturnal symptoms signal suboptimal control
• Mechanism unclear, but contributor may be ↑
parasympathetic bronchoconstrictor input to airways
“Morning dipper” per
peak flows
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Interim Summary
• Pacemaker for breathing located in the brainstem;
composed of multiple neuronal groups
• Pacemaker responds to multiple inputs
• During sleep:
• PCO2 is the main ventilatory determinant
• ↓ventilation:
• Loss of “wakefulness drive to breathe”
• ↓ chemo responsiveness
• ↑ upper airway resistance
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Interim Summary (cont)
• During REM sleep:
• Diaphragm function intact; marked reduction in
intercostal muscle activity
• Ventilatory responses to chemical stimuli most
blunted
• Clinical significance of these changes:
• Desaturations most severe in patients with lung
disease during REM
• Airways narrow during; exaggerated in asthma
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Central
Control
O2, CO2
Exchange
Ventilation
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Physiology of Respiration, 2nd ed. Hlastala MP, Berger AJ, eds. Oxford: Oxford University Press, 2001
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Inhalation
O2
Physiology of Respiration, 2nd ed. Hlastala MP, Berger AJ, eds. Oxford: Oxford University Press, 2001
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OSA
-- ---- -- -Collapsing forces (negative pressure +/- anatomic barriers ) >
distending forces (pharyngeal muscles)
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Clinical Application
Diaphragm Paralysis
Normal
Chest
Diaphragm paralysis
Abdomen
Symptoms: Dyspnea; orthopnea
Signs: Intolerance of supine positioning; thoracoabdominal paradox
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Determinants of Inspiratory Volume
• Central drive
• Neuromuscular transmission
• Strength of inspiratory muscles
• Respiratory system compliance
• Airways resistance
Work of breathing
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Compliance
• ∆ Volume/ ∆ Pressure
• ↑ compliance = ↑ distensibility
• Influenced by volume
Low
Low
High
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Respiratory System Compliance:
Lung & Chest Wall Components
Compliance influence by lung volume:
↑ lung volume→ ↓ compliance
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Conditions of ↓ Chest Wall Compliance
Obesity
Scoliosis
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Conditions of ↓ Lung Compliance
Pulmonary
fibrosis
Pleural
disease
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Airway Resistance
↑ tube radius → ↓ resistance
https://www.clinicalkey.com/
Medium-sized bronchi
provide most resistance
Airway resistance inversely influence by lung
volume: ↑ lung volume→ ↓ resistance
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Condition of ↑ Airway Resistance: COPD
Barnes PJ. N Engl J Med 2000; 343:269
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Subdivisions of Ventilation
Alveolar Ventilation = Total ventilation – Dead space ventilation



















 


Anatomic dead space











 

 


.
Vt

Amount of ventilation
devoted to gas

exchange




Alveolar dead space
Alveolar ventilation (VA)
Dead space ventilation
©2015 MFMER | slide-57
Normal Lung Ventilation
Tidal volume 500 mL
Anatomic dead space
150 mL
Frequency 15 breaths/min
Total ventilation 7500 mL/min
Dead space ventilation
2250 mL/min
Alveolar gas
3000 mL
Alveolar ventilation
5250 mL/min
Pulmonary blood flow
5000 mL/min
Adapted from: Respiratory Physiology: The Essential, 7th ed. West JB, ed. Lippincott, Williams, and Wilkins, 2007
©2015 MFMER | slide-58
Ventilation Governs PCO2
• PCO2 = VCO2
VA
CO2 production
alveolar ventilation
• PCO2 =  alveolar ventilation
•  tidal volume and/or
•  dead space
Hypoventilation results if  RR not
sufficient to augment VA
©2015 MFMER | slide-59
Causes of Hypercapnia (high PCO2)
• “Won’t breathe”
• ↓ Central drive (drugs; hypothyroidism)
• “Can’t breathe”
• ↓ Neuromuscular transmission (spinal cord
injury)
• ↓ Strength of inspiratory muscles (ALS)
• ↓ Respiratory system compliance (pneumonia)
• ↑ Airways resistance (asthma exacerbation)
Bi-level PAP may enhance alveolar ventilation
and thus overcome causes of hypoventilation
©2015 MFMER | slide-60
Clinical Application
Symptoms and Signs of Hypoventilation
• Nonspecific, insidious;
accentuated by coexistent
hypoxia
• Pulmonary hypertension
• Dyspnea not uniformly present!
• Cyanosis
• Dependent edema
• Orthopnea
• Cor pulmonale
• Elevated serum bicarbonate
• CNS effects
•
•
•
•
Altered mentation
Sleep disruption
Hypersomnolence
Headache
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Clinical Application
Evaluation for Cause(s) of Hypoventilation
• ABG: confirmatory test
• Physical exam: emphasis on thoracic, neuro systems
• Pulmonary function tests (maximal respiratory pressures)
• CXR
• Bloods: Thyroid; Ca++; Mg++; PO4; CK; aldolase; Hgb
• Diaphragm studies
• CNS imaging
• PSG
Martin TJ, Sanders MH. Sleep 1995; 18:617
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Exhalation
CO2
+
+
+
+
+
+
+
+
+
+
Physiology of Respiration, 2nd ed. Hlastala MP, Berger AJ, eds. Oxford: Oxford University Press, 2001
©2015 MFMER | slide-63
Lung Volumes and Capacities
6
Vital
capacity
5
Volume (L)
4
Tidal volume
Total
lung
capacity
3
2
1
0
Residual
volume
Functional
residual
capacity
↓ with obesity, sleep
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Obstructive Lung Disease
7
 Total
lung
capacity
6
5
Tidal
volume
Volume (L)
4
3
Slower
exhalation
time
2
 Residual
volume
 Functional
residual
capacity
1
0
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Restrictive Lung Diseases
6
5
Volume (L)
4
3
 Total lung
capacity
 Tidal volume
2
 Vital
capacity
1
 Residual
volume
 Functional
residual capacity
0
©2015 MFMER | slide-66
Interim Summary
• Main inspiratory muscle is diaphragm
• Thoracoabdominal paradox and orthopnea (shortness of
breath when supine) → diaphragmatic dysfunction
• Alveolar ventilation: balance between inspiratory load and
neuromuscular competence
• PCO2 = inadequate alveolar ventilation for metabolic
demand
• Causes:
• “Won’t breathe:” impaired central drive
• “Can’t breathe:” Dysfunction of breathing apparatus
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Summary of PFT Interpretation
TLC
FEV1
FVC
FEV1/FVC
Obstruction




Restriction



NL or 
©2015 MFMER | slide-68
Central
Control
O2, CO2
Exchange
Ventilation
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Pulmonary Gas Exchange
Normal
Terminology
V = Ventilation
Q = Perfusion
Alveolus
Diffusion
O2
CO2
Alveolar-capillary
membrane = 0.3 uM
Equilibration < 0.20 sec
Capillary
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Diffusion
Alveolus
Membrane
Capillary
Flow depends on:
-Concentration difference
-Area available for diffusion
-Thickness of membrane
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Arterial Oxygen Transport
O2 carried on
hemoglobin
in red blood
cells
O2
Normal
O2
Alveolus
O2
O2
O2
O2
O2
Capillary
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Measurements of Oxygen
• PaO2
• Pressure exerted by O2 in blood
Measured by arterial blood gas
O2
O2
O2
Artery
• SpO2
• % total hemoglobin bound with O2
Measured by pulse oximetry
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Oxyhemoglobin Dissociation Curve
100
90
80
Arterial
blood
Saturation (%)
70
60
50
40
30
Venous
blood
20
10
0
0
20
40
60
80
100
120
PaO2
©2015 MFMER | slide-74
Physiologic Mechanisms of Hypoxemia:
V/Q Mismatch
Impairment of
“V” due to
airways
obstruction
Alveolus
• Example:
• Asthma
• COPD
• Treatment
• Bronchodilators
• Steroids
Capillary
©2015 MFMER | slide-75
Physiologic Mechanisms of Hypoxemia:
V/Q Mismatch
Impairment of
“V” due to
collapse of
alveoli
Alveolus
• Example:
• Obesity
• Treatment
• Weight loss
Capillary
©2015 MFMER | slide-76
Mechanisms of Hypoxemia:
Hypoventilation
Insufficient
alveolar
ventilation
Alveolus
• Examples:
• “Can’t Breathe”
(dysfunction of
respiratory apparatus)
• ALS
• “Won’t Breathe”
(depressed respiratory
drive)
• Opioids
Capillary
• Treatment
• Bilevel PAP ± O2
• Remove respiratory
depressants
©2015 MFMER | slide-77
Mechanisms of Hypoxemia:
Shunt
Alveolus
• Examples:
• Intracardiac
• Septal defect in
heart
• Intrapulmonary
• AVM
• Hepatopulmonary
syndrome
• Treatment
• Close the defect
Blood bypasses alveoli;
cannot load O2
©2015 MFMER | slide-78
Mechanisms of Hypoxemia:
Diffusion Limitation
• Example:
• Pulmonary fibrosis
Alveolus
• Treatment
• Treat underlying
disorder
• O2
Interstitial
process
Capillary
Blood leaving alveolus fails to
reach equilibrium with alveolar
gas
©2015 MFMER | slide-79
Mechanisms of Hypoxemia:
Low Inspired Oxygen
• Example:
• High altitude
PAO2 too
O2
Alveolus
O2
O2
O2
low to drive
diffusion
• Treatment
• Descent
• O2
Capillary
©2015 MFMER | slide-80
Clinical Application:
Differentiating Causes of Hypoxemia
• Clinical scenario
• Calculate A-a gradient
• Assess response to oxygen
©2015 MFMER | slide-81
Clinical Application:
Alveolar-arterial (“A-a”) Gradient
• Measure of how well the lungs are oxygenating the
blood independent of alveolar ventilation
• PAO2: must be calculated; PaO2 measured by ABG
• PAO2 = (PB – PH2O)(FiO2) – PACO2/R
= (PB – PH2O)(FiO2) – PACO2/R
=(760-47)(.21) – 40/0.8
=150 – 50
=100 mm Hg
• A-a gradient = PAO2 – PaO2
= 100 – 90
= 10
©2015 MFMER | slide-82
Summary of Mechanisms of Hypoxemia
Clinical
scenario
 altitude;
w/o usual O2
Hypoventilation
 PCO2
Low FiO2
Diffusion
Limitation
Shunt
Abnormal
lung imaging
V/Q Mismatch
Most
common
A-a gradient
O2
responsiveness
Normal
Yes
Normal
Yes
Increased
Yes
Increased
No
Increased
Yes
©2015 MFMER | slide-83
CO2 Transport
O2
O2
Muscle
CO2
O2
CO2
In lung,
HCO3converted
back to CO2
and exhaled
O2
A
C
Capillary
A. CO2 dissolved in blood: 10%
B. CO2 attached to hemoglobin: 30%
C: Bicarbonate: 60%
B
CO2
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3Carbonic anhydrase
©2015 MFMER | slide-84
Clinical Question
• Why does the depth of desaturation vary
between disordered breathing events?
©2015 MFMER | slide-85
Interim Summary
• Alveolus is site of gas exchange
• O2, CO2 cross alveolar-capillary interface via
diffusion
• Partial pressure gradient drives the process
• Vast majority of oxygen carried in the blood by
hemoglobin
• The S-shaped hemoglobin dissociation curve:
• Physiologically advantageous
• Governs relationship between SpO2 and PaO2
• SpO2 90% = PaO2 60 mm Hg
©2015 MFMER | slide-86
Interim Summary (cont)
• Mechanisms of hypoxemia
• V/Q mismatch (most common)
• Shunt (unresponsive to supplemental O2)
• Hypoventilation (PCO2)
• Diffusion impairment (abnl lung exam, imaging)
• Low inspired oxygen
• CO2 primarily transported as HCO3-
©2015 MFMER | slide-87
Central
Control
O2, CO2
Exchange
Ventilation
©2015 MFMER | slide-88
Effects of Obesity on the Respiratory System
•  O2 consumption and CO2 production
•  ventilatory response to hypoxia and hypercapnia
• ↓ Functional residual capacity
•
•
•
•
↓ Respiratory system compliance
↑ upper and lower airways resistance
↑ V/Q mismatching
↓ lung O2 stores (deeper desats with
apneas/hypopneas)
©2015 MFMER | slide-89
Lung O2 stores = Lung volume x PAO2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
Shepard JW, Jr. Med Clin North Am 1985; 69:1243
©2015 MFMER | slide-90
• “Before I came here I was confused about this
subject. Having listened to your lecture I am still
confused. But on a higher level”
Enrico Fermi
©2015 MFMER | slide-91
Thank you for your attention!
Please e-mail if questions
• olson.eric@mayo.edu
©2015 MFMER | slide-92