Boards and Beyond: Pulmonary A Companion Book to the Boards and Beyond Website Jason Ryan, MD, MPH Version Date: 10-4-2017
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Table of Contents Pulmonary Anatomy Pulmonary Physiology Hemoglobin Pulmonary Circulation Hypoxia Ventilation & Perfusion Carbon Dioxide Lung Physical Exam Pulmonary Function Tests Obstructive Lung Disease Restrictive Lung Disease
1 4 9 14 19 22 28 33 36 38 46
Treatment of COPD/Asthma Pneumonia Pleural Disease Lung Cancer Sleep Apnea Cystic Fibrosis Tuberculosis Sarcoidosis Pulmonary Embolism Chest X-rays
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50 55 62 65 69 71 75 82 84 88
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Zones •
•
Pulmonary Anatomy
Conducting Zone •
No gas exchange
•
Large airways: nose, pharynx, trachea, bronchi
•
Filters, warms, humidifies air
Respiratory Zone •
Gas exchange
•
Respiratory bronchioles, alveolar ducts, alveoli
Jason Ryan, MD, MPH
Mucous •
Secretionsproduced by respiratory tract
•
Mostlyglycoproteinsand water Secreted by goblet cells in bronchial walls Protects against particulates, infection
•
Beating cilia move mucous to epiglottis swallowed
•
•
Alveoli •
•
•
Alveolar Cells: Pneumocytes •
•
•
Most common (97% of cells)
•
Thin for gas exchange
•
•
•
Type 2 •
Produce surfactant
•
Can proliferate to other cells – key for regeneration after injury
•
Clara cells •
Surfactant
•
Detoxification
Gas exchange Surroundedby capillaries
Surfactant
Type 1 •
Small sacs
1
Exhale alveoli shrink Could collapse atelectasis ↓ efficiency gas exchange Surfactant allows alveoli to avoid collapse
Surfactant
Surfactant •
Secreted by type 2 pneumocytes Mix of lecithins
•
Especially dipalmitoylphosphatidylcholine
•
Distending Pressure = 2 * (surface tension) radius
Neonatal respiratory distress syndrome
Fetal Lung Maturity •
Lungs are“mature” when enough surfactant present
•
Occurs around 35 weeks Lecithin–sphingomyelin ratio (L/S ratio) Both produced equally until ~35 weeks
•
Ratio >2.0 in amniotic fluid suggests lungs mature
•
•
•
•
•
•
•
Preterm delivery: betamethasone used to stimulate surfactant production in lungs
Neonatal respiratory distress syndrome •
•
•
•
Lungs collapsed (alveoli)
•
Intrapulmonary shunting
Neonatal respiratory distress syndrome
Risk factors: •
Hyaline membrane disease Atelectasis Severehypoxemia/↑pCO2(poor ventilation) Poorly responsive to O2
•
Prematurity
•
Maternal diabetes: high insulin levels decrease surfactant production
•
•
Cesarean delivery: lack of vaginal compression stress leads to reduced fetal cortisol and reduction in surfactant
Many complications Bronchopulmonary dysplasia Patent ductus arteriosus (hypoxia keeps shunt open) Retinopathy of prematurity Oxygen free radical formation •
2
•
Neovascularization in the retina
•
Retinal detachment
blindness
Aspiration •
Aspiration Foreign Body
Right lung is more common site of aspiration •
Right bronchus wider
•
Less angle
•
More vertical path to lung
•
T8
•
IVC
•
•
•
T10 •
Esophagus, Vagus nerve
Aortic hiatus •
T12
•
Aorta, thoracic duct, azygous vein
Muscles of Quiet Respiration •
•
If supine (lying flat)
Esophageal hiatus •
•
•
Right inferior lobe – lower portion
•
Right inferior lobe – superior portion
•
Right upper lobe – posterior segment
Diaphragm
Caval opening •
If upright •
Diaphragm •
•
Innervated by C3, C4, C5 (Phrenic nerve) Diaphragm irritation “referred” shoulder pain •
Classic example i s gallbladder disease
•
Also lower lung masses
•
Irritation can cause dyspnea and hiccups
Cut nerve diaphragm elevation, dyspnea •
“Paradoxical movement” Moves up with inspiration
•
Can see on fluoroscopy (“sniff test”)
Exercise Breathing
Diaphragm inspiration Exhalation is passive with normal (“quiet”) breathing
•
•
•
3
Inspiration (neck) •
Scalenes – raise ribs
•
Sternocleidomastoids – raise sternum
Exhalation (abdomen) •
Rectus muscle
•
Internal/external obliques
•
Transverse abdominis
•
Internal intercostals
Use of accessory muscles in respiratory distress
Physiology Concepts 1. 2. 3. 4. 5.
Pulmonary Physiology
Lung volumes/capacities Ventilation and dead space Lung and chest wall pressures Lung compliance Air flow resistance
Jason Ryan, MD, MPH
Lung Capacities
Lung Volumes •
•
•
•
•
Capacity = sum of two volumes
Tidal volume
•
Total lung capacity
•
Inspiratory capacity
In/out air with each quiet breath
Expiratory reserve volume •
Extra air pushed out with force beyond TV
•
RV remains in lungs
Sum of all volumes
•
RV + ERV+ IRV + TV
•
•
Inspiratoryreservevolume •
Extra air can be drawn in with force beyond TV
•
Lungs filled to capacity
•
Residual volume •
•
Most air you can inspire TV + IRV
Vital capacity •
Most you can exhale
•
TV + IRV + ERV
Air that can’t be blown out no matter how hard you try
Lung Capacities Capacity = sum of two volumes •
RV ERV IRV TV
4
Functional Residual Capacity •
Residual volume after quiet expiration
•
RV + ERV
•
Volume when system is relaxed
•
Chest wall pulling out = lungs pulling in
Ventilation •
Dead Space
Ventilation = volume x frequency (resp rate) •
500cc per breath x 20 breaths per minute
•
10,000cc/min
•
Alveolar ventilation = useful for gas exchange
•
Dead space ventilation = wasted ventilation •
•
Space filled with air but no gas exchange #1: Anatomic dead space
•
#2: Physiologic dead space
•
Nose, trachea, other areas with no gas exchange
•
Ventilation •
•
•
•
**Volume in slightly > volume out due to O2 uptake Sometimes called minute ventilation
Alveolar ventilation •
Fresh air for gas exchange
•
TV minus “dead space”
Imagine 500cc out per minute •
150cc fills dead space
•
Only 350cc available for gas exchange
Volume of conducting portions respiratory tract
•
Nose, trachea
•
Anatomic PLUS volume of alveoli that don’t exchangegas
•
Insufficient perfusion
•
Apex is largest contributor
Physiologic dead space increases many diseases
Measuring Dead Space
Total ventilation (TV) = volume/min out eachbreath •
•
•
Bohr’s method
•
Physiologic dead space (Vd) from: •
Tidal volume
•
PeCO2 (exhaled air)
•
PaCO2 (blood gas)
Vd = PaCO2 – PeCO2 Vt PaCO2
Lung and Chest Wall
Pressures Patm = 760mmHg or 0mmHg
•
Lungs tend to collapse
•
Chest wall tends to expand
•
•
Pull inward/recoil
= 0 No Flow
Spring outward Patm = 760mmHg or 0mmHg
Alveoli
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Pressures
Pressures Patm = 760mmHg or 0mmHg
Patm = 760mmHg or 0mmHg
= +5 Flow Out
= +5 Flow In
Patm = 765mmHg or +5mmHg
Patm = 755mmHg or -5mmHg
Alveoli
Alveoli
Lung Volumes and Pressures
0
20
Chest Volumes and Pressures
40
-40
-20
Pressure
•
Lung in = chest out Volume where lungs rest after quiet exhalation
•
Pressure inside system is zero
•
Lungs
•
•
FRC
System 0
20
40
Functional residual capacity
Chest Wall
-20
20 Pressure
Chest Volumes and Pressures
-40
0
40
Pressure
6
No ↑/↓ pressure from push/pull of lungs or chest wall Pressure = atmospheric pressure
Alveoli and PleuralPressures
Pressures
Quiet (tidal) breathing Inhale
+
Exhale Alveoli
0
Alveoli Pleural Space
Intrapleural
Chest Wall
Transpulmonary Pressure •
Transpulmonary Pressure
AlveolarPressure – IntrapleuralPressure
•
AlveolarPressure – Intrapleural Pressure
+5 +5 +5
0 30
TPP = +5 – (+5) = 0
Forced Exhalation •
•
•
•
(+) Pressure: Holds airway open (-) Pressure: Airway collapse
-30
Equal Pressure Point
Pleural pressure becomespositive
•
Compresses airway Pressure on alveoli positive pressure in airway
Pushes air out
TPP = 0 – (-30) = +30
•
•
•
air flows from airways
Pleural pressure = airway pressure Beyond this point airway collapses In healthy lungs: EPP occurs incartilaginousairways Preventsairwaycollapse
Pleural Pressure + Elastic Recoil
+ + + +90 + +60 + + + + +
+ + + + + + ++ +
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+60 +75
+60 +60
Equal Pressure Point •
Lung Compliance
Disease: EPP moves toward alveoli
•
•
Obstruction (bronchitis): more pressure drop
•
Emphysema: loss of elastic recoil
•
Can be reached in thin-walled bronchioles
•
Result: Collapse, obstruction to airflow, air trapping
•
+60
+ ++ +75 +60 + +90 +
•
For given pressure how much volume changes Compliant lung •
Small amount diaphragm effort
•
Generates small pressure change across lungs
•
Large volume change
•
Easy to move air in/out
Non-compliant lung •
Large amount diaphragm effort Big pressure change across lung
•
Small volume change (lungs stiff)
•
Hard to move air in/out
•
+60
+ ++ +
ΔP
+60
Lung Compliance
Lung Compliance
•
Normal lung
Non compliant lung •
Decreased •
Pneumonia
•
Pulmonary edema
•
Pulmonary fibrosis
Increased •
•
20
0
40
Resistance to Air Flow •
Upper airways about 50% resistance
•
Lower airway resistance
•
C=ΔV
Nose, mouth, pharynx
•
Highest in medium bronchi (turbulent flow)
•
Lowest in terminal bronchioles - slows laminar flow Trachea
Terminal bronchioles Medium Bronchi
Air vessel size
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Emphysema (floppy lungs) Aging
C=ΔV ΔP
Hemoglobin •
Globin chains
•
Heme
•
Polypeptides
•
4 chains in 2 pairs
•
Molecule (non-peptide)
Hemoglobin Jason Ryan, MD, MPH
Globin Protein Types •
Alpha (α) Beta (β)
•
Gamma (γ)
•
•
Hemoglobin Types •
Delta (δ)
•
Hemoglobin A •
Adult type
•
Most common type found (95%)
•
α2 β2
Hemoglobin A2 •
•
Fetal Hemoglobin •
•
•
•
•
Adult type Less common type (2-3%)
•
α2 δ2
Hemoglobin F •
Fetal type
•
α2 γ2
Globin Chain Diseases
HbF(α2γ2) •
•
After 8 weeks HbF is predominant Hb Up to 90% fetal hemoglobin Levels fall in weeks/months after birth
•
α-thalassemia
•
β-thalassemia minor/major
•
Sickle Cell Anemia
•
•
In adult HbF <1% total hemoglobin Higher O2 affinity than HbA
•
Helps transport oxygen from maternal circulation
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Underproduction alpha chain
Underproduction beta chain HbS production
2,3-Bisphosphoglycerate
Heme •
•
•
2,3 BPG
Molecule with iron (Fe) in the middle Ring around Fe called a porphyrin
•
Promotes O2 release from hemoglobin Increasing levels:
•
More BPG at high altitude
Oxygen bindsiron
2,3 Bisphosphoglycerate •
Created from diverted 1,3 BPG (glycolysis)
•
Sacrifices ATP fromglycolysis
Found in RBCs
•
•
•
Decrease oxygen affinity of hemoglobin
•
Increase delivery oxygen to tissues
Hemoglobin Forms •
Taut form (T) •
Low O2 affinity Tends to release O2
•
Favored form in tissues
•
Glyceraldehyde-3-phosphate •
Relaxed form(R) •
2,3 BPG
1,3-bisphosphoglycerate BPG Mutase 3-phosphoglycerate
•
2 affinity High Oon Holds to O 2
•
Favored form in lungs
2-phosphoglycerate Phosphoenolpyruvate Pyruvate
Hemoglobin Forms •
Tissues •
•
•
•
•
Dissociation Curves
Low pH High H+, CO 2 Favors the T form
100
O2 released for use
75
Lungs •
High pH
•
Low H+, CO 2 Favors R form
•
Binds O2 to carry to tissues
•
50 25 25
50
75
pO2 (mmHg)
10
100
Cooperativity •
•
•
Allosteric Effects
Four heme groups do not undergo simultaneous oxygenation First O2 molecule that binds INCREASES affinity of hemoglobin for 2nd molecule Makes curve S shaped
Hemoglobin is an allosteric structure
•
Cooperativity is a positive allosteric effect
Easier to release O2
pH
•
Temperature 2,3 BPG
•
CO2
•
•
Right Curve Shifts
Hgb Allosteric Effectors •
•
Allosteric proteins change affinity for binding when influenced by other (smaller) molecules Usually multi-subunitproteins
•
100
75
Right Shift +
50
↑Co2, BPG, Temp, H
25 25
50
75
100
pO2 (mmHg)
Left Curve Shifts
Fetal Hemoglobin
Harder to release O2
HbF(α2γ2)
100
100
75
75
Left Shift ↓Co2, BPG, Temp, H+
50
Left Shift Higher O2 affinity
50
25
25 25
50
75
100
25
pO2 (mmHg)
50
75
pO2 (mmHg)
11
100
Carbon Monoxide •
•
• •
Carbon Monoxide
Binds to iron in heme 240x the affinity of oxygen Blocks O2 binding sites (less O2 can be absorbed) Other binding sites cannot offload O 2 •
Allosteric modification of hemoglobin
•
Shifts dissociation curve left
Normal
100
75
carrying capacity
50% CO Hb 50
Left shift
25 25
50
75
100
pO2 (mmHg)
Carbon Monoxide Poisoning •
•
•
•
Carbon Monoxide Poisoning
Nonspecific symptoms
•
Standard pulse oximetry normal
Headache most common Malaise, nausea, dizziness Classic (but rare) sign: Cherry red lips
•
Diagnosis: carboxyhemoglobin level
•
•
•
Carboxyhemoglobin is red •
Methemoglobinemia •
Iron in hemoglobin normally reduced (Fe2+) Certain drug oxidize iron to Fe3+
•
When Fe3+ is present methemoglobin
•
•
•
Fe3+ cannot bind oxygen Remaining Fe2+ cannot release to tissues
•
Normal <3%
•
Smokers 10-15%
•
Do not see blue lips (cyanosis)
Cannot differentiate carboxyhemoglobin/oxyhemoglobin
>15% suggest poisoning
Treatment: Oxygen
Methemoglobinemia •
•
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Acquired methemoglobinemia from drugs •
Local anesthetics (benzocaine)
•
Nitric oxide
•
Dapsone
Treatment: methylene blue
Clinical Scenario •
•
•
•
•
•
•
Cyanide Poisoning
Endoscopy patient
•
Benzocaine spray used for throat analgesia Post procedure shortness of breath
“Chocolatebrownblood” O2 sat (pulse oximetry) = variable (80s-90s) PaO2 (blood gas) = normal Also premature babies given NO for pulmonary vasodilation
Cyanide Poisoning Treatment •
•
Nitrites (amyl nitrite, sodium nitrite) •
Generate methemoglobin
•
Contains Fe3+ which cyanide binds
•
Pulls cyanide away from mi tochondria
Hydroxocobalamin •
•
•
Precursor of vitamin B12 Binds to intracellular cyanide forming cyanocobalamin
•
Readily excreted in the urine
Thiosulfate (sodium thiosulfate) •
Transforms cyanide to thiocyanate
•
Thiocyanate then renally excreted
13
Cyanide binds to Fe3+ in cells
•
Blocks electron transport chain in mitochondria Aerobic metabolism stops
•
Anaerobic metabolism occurs
•
Lactic acidosis occurs
•
•
Functional hypoxia
•
Especially bad for brain and heart
Pulmonary Circulation
Pulmonary Circulation
Right Ventricle
Pulmonary Artery
Capillaries (Alveoli)
Pulmonary Veins
Jason Ryan, MD, MPH
Pulmonary Circulation •
•
Blood O2 Content
Low pressure system •
Systemic: 120/80
•
Pulmonary artery: 24/12
•
Systemic circulation
•
Pulmonarycirculation
•
Walls of pulmonary artery very thin •
•
•
Little smooth muscle Low resistance to flow Very distensible (compliant) •
↓ O2 level (PaO2) leads to vasodilation (↑blood flow)
•
↓O2 level (PaO2) leads to vasoconstriction (↓blood flow) “Hypoxic vasoconstriction”
•
Shunts blood away from poorly ventilated areas
•
More blood to well ventilated areas
•
Key for fetal circulation •
Low O2 constricts pulmonary arteries in womb
•
At birth, arteries receive O2 and dilate
Diffusion
Blood O2 Content Lungs
•
•
w lo F d o lo B ystemic
PaO2
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Gases must diffuse from air to blood Rate of diffusion depends on: •
Pressure difference (air-blood)
•
Area of alveoli for diffusion
•
Thickness of alveolar tissue
Left Atrium
Diffusion
Diffusion Vgas = Area * D * (P1- P2) Thickness P2
P1
•
Area falls in emphysema
•
Thickness rises in pulmonary fibrosis
•
Both lead to poor diffusion hypoxia
Thickness
Diffusion-Perfusion Limitations
Diffusion Limitations
N2O
PA
Partial Pressure
O2
e r u
For [gas] in blood to rise: #1: Gas must diffuse #2: Perfusion must carry gas away
s s e r P
#3: Cannot dissolve in blood
ali t r a
CO
P
Length along capillary
Carbon Monoxide
Nitrous Oxide (N2O)
Diffusion Limited
Perfusion Limited
Partial Pressure
Partial Pressure
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Diffusion-Perfusion Limitations
Oxygen
N2O
•
Normal healthy subjects: O2 uptake perfusion limited
•
Disease (i.e. fibrosis, emphysema):diffusionlimited
PA O2
e r u
For [gas] in blood to rise: #1: Gas must diffuse #2: Perfusion must carry gas away #3: Cannot dissolve in blood
s s e r P l iat r
CO
Pa
Length along capillary
DLCO Diffusing capacity of carbon monoxide •
•
•
Measures ability of lungs to transfer gas
•
•
Healthy
PA
Patient inhales small amount (not dangerous) CO CO uptake isdiffusion limited •
•
O2 Diffusion-Perfusion
e
Disease
r u
Amount taken up ≈ diffusion functionlungs s s re
Machine measures CO exhaled P ali
Normal = 75 – 140% predicted Severe disease <40% predicted t r a P
Length along capillary
O2 Diffusion-Perfusion PA
Rest
Pulmonary Vascular Resistance Resistance to blood flow •
Two vessels: alveolar and arteriolar
•
Increased lung volumes stretch alveolar vessels
Exercise
e r u se
•
r P l
•
Makes them longer with smaller diameter
•
Increases resistance
Decreased lung volumes narrow arteriolar vessels •
iat
Increases resistance
r
Exhale a P
PVR Length along capillary
FRC
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Inhale
Pulmonary Hypertension •
•
Normal PA pressure •
24/12
•
Mean 10-14mmHg
•
•
Pulmonary hypertension •
•
Pulmonary Hypertension
Mean pressure >25mmHg
Loud P2 = pulmonary hypertension
Main symptom is dyspnea Untreated can lead to“cor pulmonale” •
Chronic high pressure in ri ght ventricle
•
Right ventricle hypertrophies
•
Eventually dilates and fails
•
Jugular venous distension Lower extremity edema
•
Look for accentuated or loud second heart sound
•
•
Left upper sternal border
•
•
Pulmonary Hypertension •
Gold standard for diagnosis: right heart cath
•
Non-invasive diagnosis byechocardiography •
Estimate PA pressure
•
Visualize right heart structures
Hepatomegaly
Death from heart failure or arrhythmia
Pulmonary Hypertension Ohm’s Law V = I R For fluids: P = Q X R For lungs: P = CO * PVR
P = PPA – PLA = CO * PVR PPA = CO * PVR + PLA
Pulmonary Hypertension
Pulmonary Hypertension
•
High PVR “Pulmonary Arterial HTN” Primary or Secondary
Secondary causes high PVR •
COPD
•
Chronic pulmonary emboli
•
Pulmonary fibrosis (scleroderma)
•
PPA = CO * PVR + PLA High Flow States Left to right shunts ASD/VSD/PDA
•
High LA Pressure Most common cause PHTN “Pulmonary Venous HTN” Heart Failure Valve Disease
17
Sleep apnea or high altitude (chronic hypoxia) HIV
1° Pulmonary Hypertension •
•
•
•
•
•
1° Pulmonary Hypertension
Rare disease
•
Classically affects young women Increased endothelin (vasoconstrictor) Decreased NO
•
Progressive dyspnea and right heart failure if untreated Treatments (all lower PVR): •
Epoprostenol: Prostacyclin (IV)
•
Bosentan: Antagonist endothelin-1 receptors (PO)
•
•
Bone morphogenetic protein receptor type II
•
Up to 25% of idiopathic cases
•
Up to 80% familial cases
•
Vasoconstriction, smoothmuscle proliferation Highpulmonarypressures
1° Pulmonary Hypertension •
Associated with BMPR2 gene mutations
Sildenafil: Inhibits PDE-5 in smooth muscle of lungs (PO)
18
Abnormal endothelial and vascular smooth muscle growth/proliferation
Oxygen delivery to tissues •
•
Delivery = Cardiac Output * O 2 Content of blood For proper O2 delivery need: •
Normal cardiac output
•
Normal O2 content
Hypoxia Jason Ryan, MD, MPH
What determines O2 content? •
#1: O2 binding capacity •
•
•
How much O2 blood can hold Determined by hemoglobin
•
Partial pressure oxygen in blood
•
Obtained from an arterial blood gas
•
#2: % Saturation •
•
PaO2
•
% Hemoglobin molecules saturated
Reflects amount of O 2 dissolved in blood Normal: >80mmHg
#3: O2 O2Dissolved directly dissolved in blood •
Pulse Oximetry •
• •
Oxygen Content
Measures % O2 saturation of blood Related to PaO2 Uses light and a photodetector
O2 Content = (O2 Binding Capacity ) * (% Sat) + (Dissolved 2O) (ml O2/dl)
(1.39 * Hb)
•
19
Normal O2 content requires: •
Presence of hemoglobin
•
Saturation of hemoglobin
•
Normal PaO2
0.003 PaO2
Hypoxemia, Hypoxia, Ischemia •
•
•
Hypoxemia, Hypoxia, Ischemia
Hypoxemia: Low oxygen content of blood
Heart Failure •
•
•
•
•
Low O2 sat or low PaO2 = hypoxemia Hypoxemia hypoxia
•
Can have hypoxia without hypoxemia (normal O2 sat)
•
Hypoxia: Low O2 delivery to tissues Ischemia: Loss of blood flow
Anemia
↓ cardiacoutput
↓ blood flow to tissues hypoxia O2 content of blood may be normal PaO2 and O2 sat may be normal
•
Oxygenation of blood by lungs is normal
•
Oxygen carrying capacity of blood reduced
•
•
Low O2 content of blood PaO2 and O2 sat normal
O2 Content = (O2 Binding Capacity ) * (% Sat) + (Dissolved 2O) O2 Content = (O2 Binding Capacity ) * (% Sat) + (Dissolved 2O)
Normal PaO2
Carbon Monoxide •
Binds to iron in heme - 240x the affinity of oxygen
•
Blocks O 2 binding sites:“Functionalanemia” Alveolar O2 (PAO2) usually normal
•
Normal PAO2 Normal PaO2
•
•
•
Amount of CO gas required for poisoning usually small
↓ O2 binding to Hb despite normal PaO2
•
Low O2 sat (CO blocking O2 binding sites) Pulse oximeter shows normal (100%) O 2 sat
•
O2 content of blood reduced
•
Causes of Hypoxia
Low O2 % sat (reality) Normal O2 % sat (detector) Hypoxia
•
Can’t distinguish Hb bound to CO from that bound to O2
20
Alveolar Gas
Alveolar Gas Equation
Inspired Air PIO2 (150mmHg)
•
PIO2 ≠ PAO2 •
Alveoli PAO2(100mmHg)
Due to mixing of alveolar oxygen with CO2
PAO2 = PIO2 – PaCO2 = 150 – PaCO2 R
0.8
Arterial Blood PaO2 (90mmHg)
A-a Gradient • •
• •
• •
A-a Gradient
Difference between alveolar (A) and arterial (a) 2O Helpful for evaluating hypoxemia Step 1: Measure PaO2,PaCO2 Step 2: Determine PAO2from gas equation Step 3: A-a gradient = PAO2– PaO2
Hypoxemia with normal A-a gradient
•
Hypoventilation
Normal 10-15mmHg •
Shunting from thebesian and bronchial veins
A-a Gradient •
•
Hypoxemia with high A-a gradient •
•
•
Alveoli not working
Can’t get O2 to blood Blood not going to working alveoli
•
Most lung diseases have high A-a gradient
•
Three basic mechanisms create the highA-a gradient
•
Pneumonia, pulmonary edema, etc.
•
Fibrosis
•
Shunt
•
V/Q Mismatch
21
•
Alveoli working
•
Not inhaling enough O2
•
Reduced respiratory rate
•
Reduced tidal volume
•
Narcotics, neuromuscular weakness, obesity
•
High altitude
•
Can treat with more oxygen
A-a Gradient •
Hypoxemiawith high A-a gradient
•
Three basic mechanisms create the high A-a gradient
•
•
Ventilation & Perfusion
•
Jason Ryan, MD, MPH
Diffusion Limitation •
Increased A-a gradient
•
Hypoxemia
• •
•
•
Ventilation without perfusion
•
Dead space may cause hypercapnia
•
Reduced ventilation relative to perfusion Perfusion wasted
•
Blood going where not enough O2 present
#2: Shunt
•
#3: V/Q Mismatch
Dead space hypercapnia (↑CO2)
Ideally ventilation to lung is matched by perfusion
•
Normal lungs:
•
•
Ideal V/Q = 1
•
4L/min air into lungs
•
5L/min blood into lungs
•
V/Q < 1 •
#1: Diffusion limitation
•
•
Hypoxemia Hypercapnia Destruction alveolar capillaries dead space
•
•
Ventilation-Perfusion
Less effect on CO 2 Seen in pulmonary fibrosis •
Alveoli can’t get O2 to blood Blood not going to working alveoli
V/Q = 0.8
If V/Q too high or too low, ventilation is inefficient
Shunting •
Extreme reduction in V/Q V/Q = 0
•
Venous blood to arterial system without oxygenation
•
•
22
Causes hypoxemia
Shunting
Shunting •
Anatomic shunting
•
Physiologic shunting
•
Blood bypasses lungs/alveoli completely
•
Intra-cardiac, pulmonary AVMs
•
Blood goes to alveoli that don’t work
•
Non-ventilated alveoli are perfused
•
One example: Atelectasis (collapsed airway)
99%
99% O2 = 99%
Shunting
V/Q > 1
↑ RR from ↓ O2 Won’t help PaO2 Will keep CO2 normal
V/Q = 0
•
Reduced perfusion relative to ventilation
•
Ventilation wasted
•
Gas going in where insufficient blood flow
99%
<99% O2 < 99%
Dead Space •
Extreme increase in V/Q V/Q =∞
•
Anatomic dead space
•
•
Dead Space •
Physiologic dead space increases many diseases Poor perfusion of alveoli
•
Fibrosismay cause dead space
•
•
Volume of conducting portions respiratory tract
•
Destruction of alveolar capillaries
•
Nose, trachea
•
Alveoli ventilated but under-perfused
Physiologic dead space •
Anatomic PLUS volume of alveoli that don’t exchangegas
•
Insufficient perfusion
•
Apex is largest contributor
23
Dead Space
V/Q Mismatch
V/Q = ∞ Main problem: ↑ CO2 May lead to hypoxemia if V/Q mismatch occurs
•
Intermediate state •
Some lung areas low V/Q
•
Others high V/Q
•
Inadequate ventilation Reduced oxygenation of blood
•
↑ RR CO2 normal
•
V/Q = 0
V/Q Mismatch
Shunt
99%
V/Q = ∞
Dead Space
O2 = 99%
V-Q Mismatch
Inadequate Gas Exchange
Pulmonary Edema
V/Q < 1
•
Caused by shunt, V/Q mismatch, dead space
•
Determination of underlying mechanism: •
#1: Response to 100% oxygen
•
#2: Hypercapnia (↑CO2)
99%
<99% O2 < 99%
100% Oxygen •
•
• •
Shunting
Shunting (V/Q=0) won’tcorrect with 100% oxygen
V/Q = 0
Functioning alveoli extracting maximum 2O Increase alveolar O2 does not help Sick alveoli do not receive 100% O2 (↓V)
100% O2
99%
<99% O2 < 99%
24
100% Oxygen
Dead Space
•
Dead space will correct with 100% oxygen
•
V/Q mismatch will correct with 100% oxygen
•
Increasing O2 content in alveoli Increased PaO2
V/Q < 1
V/Q = ∞
21% O2
<99%
O2 < 99%
V/Q Mismatch
Dead Space
Pulmonary Edema
V/Q < 1
V/Q < 1
V/Q = ∞
100% O2
21% O2 99%
99%
<99%
O2 99%
O2 < 99%
V/Q Mismatch
Hypercapnia
Pulmonary Edema
•
V/Q < 1
Causes of elevated PaCO2 •
Increased production (fever)
•
Decreased ventilation (hypoventilation)
•
Increased dead space
100%
100% O2
CO2 production PaCO2 α 99%
99% O2 = 99%
25
CO2 production =
Alveolar Ventilation
Tidal Vol – Dead Space
Hypercapnia •
Dead space: classic cause of hypercapnia
•
Perfusion problem Ventilation wasted
•
Elevated PaCO2
•
Hypercapnia •
•
•
•
•
CO2 production PaCO2 α
Shunting and V/Q mismatch rarely cause↑ PaCO2 Increased ventilation resolves hypercapnia Hypoxemia ↑ RR ↑ alveolar ventilation Healthy alveoli able to compensate Normal CO2excretion
CO 2 production =
Alveolar Ventilation
Tidal Vol – Dead Space
PaCO2
CO2 production
CO 2 production =
Alveolar Ventilation
Mechanisms of Hypoxemia
Tidal Vol – Dead Space
Ventilation-Perfusion
High A-a gradient
Apex Less Blood Flow Less Ventilation
Both decrease bottom to top Blood flow decreases more V/Q ratio changes
Base Most Blood Flow Most Ventilation
Mechanisms by Disease
Ventilation-Perfusion Apex V/Q > 3 Lots of Ventilation (relative) High O2, Low CO2
•
•
Overall V/Q = 0.8
Base V/Q <0.6 Low Ventilation (relative) Low O2, High CO2
26
Most diseases (COPD, PNA, CHF) have hypoxemia from multiple mechanisms •
PNA may cause V/Q mismatch or shunt
•
COPD may cause alveoli and blood vessel destruction
Some examples worth knowing •
Intra-cardiac shunt: Pure shunt mechanism
•
Inhale a peanut: V/Q = 0
•
Pulmonary Embolism: V/Q = ∞
Ventilation-Perfusion •
Lung Pressure Zones
With exercise overall V/Q approaches 1 •
More blood flow
•
More ventilation
•
↑ ventilation > ↑blood flow
•
Because of gravity, more pressure in artery (P a) and veins (Pv) at bottom compared to top of lungs •
•
•
•
This compresses vessels
•
Less blood flow/perfusion
•
•
Pressure Zones a
A
v
Zone 1 (Apex) PA > Pa > Pv
Zone 2 (Mid) Pa > PA > Pv
Zone 3 (Base) Pa > Pv > PA A a
v
27
As you move up lungs, Pa and Pv fall
Alveolar pressure (PA) same throughout lung In theory, PA at apex can become > Pa /Pv
Very high V/Q More dead space
Carbon Dioxide •
Produced by cellular metabolism
•
Transported to lungs via 3 mechanisms •
Bicarbonate (90%)
•
Bound to hemoglobin (5%)
•
Dissolved (5%)
Carbon Dioxide Jason Ryan, MD, MPH
Bicarbonate
Bohr Effect
•
Red blood cells contain carbonic anhydrase
•
H+ can bind to hemoglobin
•
Converts CO2/H2O to HCO3-/H+
•
Binds to end of globin chains not heme
•
•
CO2 + H2O H2CO3 HCO3 -+ H +
Converts Hb to taut form which releases O2 Shifts O2 curve to right
CO2 + H2O H2CO3 HCO 3- + H+ HHb Hb
Bohr Effect
Bohr Effect
Easier to release O2
Easier to release O2
100
100
75
75
50
50
25
25 25
50
75
100
Low H+ (lungs) High H+ (tissues)
25
pO2 (mmHg)
Right Shift More O2 offloaded for given PO2
50
75
pO2 (mmHg)
28
100
Chloride Shift •
• •
•
Carbaminohemoglobin
RBCs convert CO2 to HCO3- via carbonic anhydrase HCO3- inside RBCs leaves cell to plasma Cl- enters cell to maintain electrical neutrality RBCs have high Cl- content in venous blood
CO + H O H CO 2
2
2
3
•
•
•
Hemoglobin bound to CO2 In low O2 environment Hb more likely to bind CO 2 Haldane Effect
HCO -+ H + 3
Cl-
Haldane Effect
Haldane Effect Low O2 (tissues)
High O2 (lungs)
Hb
CO2
CO2 Content
Content
Low
High
Low
PCO2
CO2 in Special Situations
Tissues vs. Lungs Tissues • • •
•
•
Low O2 (consumption) High CO2 (metabolism) +
High H Favors O2 unloading (Bohr Effect) Favors CO2 loading (Haldane Effect)
High PCO2
Lungs • • •
•
•
•
HighAltitude Exercise
•
Cerebral Blood Flow
•
High O2 (air) Low CO2 (air) +
•
Low H Favors O2 loading (Bohr Effect) Favors CO2 unloading (HaldaneEffect)
29
Control of Respiration
High Altitude •
• •
• • •
Lower atmospheric pressure
High Altitude
pH ↑ pO2 ↓ pCO2 ↓ HCO3 - ↓
Lower pO2 Hypoxia hyperventilation ↓pCO2 respiratory alkalosis (pH rises) After 24-48hrs, kidneys will excrete HCO3pH will fall back toward normal
•
↑ erythropoietin
•
Chronichypoxic vasoconstriction
•
High Altitude
Will raise Hct and Hgb over 10-14 days
•
Pulmonary hypertension
•
Can lead to RVH
High Altitude Cumulative Effect
•
•
•
Changes to O2 dissociation curve Alkalosis causes leftward shift Also stimulates production of 2,3 BPG •
•
Alkalosis
100
↑ 2,3 BPG
75
Increased levels when RBCs need to release more O2
This shifts curve back toward normal position 50
25 25
50
75
pO2 (mmHg)
Exercise •
• •
Exercise
↑ O2 consumption ↑ CO2 production ↑ ventilation
•
• •
More CO2 produced by muscles CO2 levels in venous blood rise More O2 consumed by muscles
•
O2 levels in venous blood fall
30
100
O2 Diffusion-Perfusion
Exercise •
↑ ventilation and blood flow
•
Normal PaO2 and PaCO2 despite metabolic changes
Rest
e
Exercise
r u s s e r P l iat r Pa
Veins: O2 falls, CO2 rises Arteries: O2 and CO2 normal
Length along capillary
Panic Attacks
Cerebral Blood Flow
•
•
•
•
Normal Range
O2 Content
Normal Range
•
PaCO2 is the major stimulus for breathing Central chemoreceptors in medulla most important
•
Peripheral chemoreceptors: carotid and aortic bodies •
•
•
Low CO2 Hypocapnia cerebral vasoconstriction CNS symptoms (dizziness, blurred vision)
CO2 Content
CO2 and Breathing Control •
Hyperventilation
CO2 and Breathing Control •
COPD patients chronically retain CO 2 Response to CO2 can become blunted Oxygen level then becomes major stimulus
•
Classic scenario:
•
•
Can sense CO2 but more sensitive to O2
High PaCO2 increased respiratory rate Low PaCO2 decreased respiratory rate
•
31
Sensed by peripheral chemoreceptors
•
COPD patient
•
100% oxygen applied for dyspnea
•
Respiratory depression
CO2 and Breathing Control •
• •
CO2 and Breathing Control
Oxygen can mask hypoventilation
•
High CO2 level useful to determine ventilation status Clinical scenario: •
•
•
•
Patient with pneumonia
•
O2 applied via nasal cannula O2 level 95%
•
Blood gas: PaCO2 = 60mmHg (high)
•
Clinical scenario
•
•
O2 saturation on O2 95% Blood gas: PaCO 2 = 60 (high) Respiratory muscles failing
Symptoms of high CO2 •
•
•
32
Patient with neuromuscular disease (ALS)
Lethargy Confusion Agitation
Lung Exam •
Percussion
•
Auscultation
•
Lung Physical Exam
•
Jason Ryan, MD, MPH
•
•
•
Normal sounds = resonant
•
Abnormal: dull or hyperresonant Dull •
Pleural effusion
•
Consolidation (pneumonia)
•
•
Pneumothorax
•
Emphysema
•
Rales Wheezes
•
Rhonchi
•
•
Upper, mid, lower lung fields
Special techniques •
Fremitus
•
Pectoriloquy
Normal breath sounds are vesicular Most all pathologic lung processes result in decreased lung sounds over affected area
Hyperresonant air trapped
Adventitious Lung Sounds •
Stethoscope thorax
•
Lung Auscultation
Percussion •
Finger against thorax tap
•
Rales •
Also called crackles Small airways “pop” open after collapse
•
Earlyinspiratory,lateinspiratoryor expiratory
•
•
Bronchial breath sounds Stridor
33
Classiccauses •
Pulmonary edema (bases)
•
Pneumonia
•
Interstitial fibrosis
Wheezes •
•
•
•
Rhonchi
Air flows through narrowed bronchi Usuallyexpiratory orinspiratory/expiratory Classic cause is asthma Other causes: •
Heart failure (cardiac asthma)
•
Chronic bronchitis
•
Obstruction (tumor; localized wheeze)
Bronchial Breath Sounds •
•
•
•
•
Secretions in large airways
•
Course breath sounds
•
Classic cause is COPD
Stridor
High pitched lung sounds Like flow through tube
•
•
Longer expiratory phase than normal Seen in pneumonia with consolidation
•
•
Wheeze that is almost entirely inspiratory Usually loudest over neck Indicates partial obstruction of larynx or trachea Some classic causes •
Pectoriloquy •
Sounds over chest through stethoscope Bronchophony
•
Whispered pectoriloquy
•
•
Epiglottitis (Hib in children) Retropharyngeal abscess
•
Diphtheria
Fremitus
Whispered “99-99-99”
•
Should be muffled
•
Abnormal if clear
•
Egophony: “Eeeeee” sounds like“Aaaay”
•
All indicated fluid in lungs: Effusion, consolidation
•
Place hands on patients back Patientsays “ninety-nine”
•
Vibrations travel through airways to back
•
Voice sounds are louder and clearer
•
Laryngotracheitis (croup)
•
•
•
•
•
34
Varies with density of lung tissue Only common condition with increased fremitus is lobar pneumonia Decreased in most other processes •
Pleural effusion
•
Pneumothorax
•
Atelectasis
Nail Clubbing •
•
•
•
•
•
Associated with many pulmonary diseases Bronchiectasis CysticFibrosis Lungtumors Pulmonaryfibrosis Also heartcyanotic disease congenital
35
Dyspnea
Pulmonary Function Tests
•
Many, many causes
•
Deconditioning
•
Anemia
•
Pulmonary causes
Jason Ryan, MD, MPH
Pulmonary Dyspnea •
•
Pulmonary Function Testing
Obstruction •
Can’t get air out of lungs
•
Air trapped
•
Poor oxygenation
•
•
Helps determine disease severity/progression •
Sometimes unclear from history, exam, x-ray, etc. Many diseases monitored by PFTs COPD, Pulmonary Fibrosis
Spirometry FVC
Method for assessing pulmonary function •
Helps determine cause of dyspnea
•
Can’t get air into lungs Poor oxygenation
Spirometry •
Determining flows, volumes in lung
•
•
Restriction •
•
Pulmonary function tests (PFTs)
•
Patient blows into machine
•
Volume of air measured over time
FEV1
Normal FVC = 5L FEV1 = 4L FEV1/FVC = 0.8
1
Time (s)
36
Spirometry
Spirometry Normal
Normal
FEV1
Restrictive Obstructive
Restrictive Obstructive
FEV1
FEV1
1
1
Time (s)
Time (s)
Spirometry
Summary
FVC
Normal
FVC FVC
Restrictive Obstructive
•
•
FEV1 and FVC fall in both obstructive and restrictive diseases FEV1 falls MORE than FVC in obstructive
1
Time (s)
Volumes •
•
•
•
Spirometry with Volumes
Spirometry can measure •
VC (FVC)
•
IRV
•
ERV
6
FVC FEV1
Cannot measure •
RV
•
FRC
Residualvolumerarely measured clinically Requiresspecial techniques 1
Time (s)
37
Spirometry with Volumes
Flow Volume Loop
Obstructive
Normal Restrictive
Volume (L)
1
Time (s) Image courtesy of SPhotographer
Flow Volume Loop
Work of Breathing •
Work proportional to resistance
Image courtesy of SPhotographer
Work of Breathing •
Airflow resistance: Slower you breathe, less resistance
Work of Breathing •
Elastic resistance: Faster you breathe, less resistance
Air Flow
Elastic 15
15
Breaths per minute
Breaths per minute
38
Work of Breathing
Work of Breathing
•
Slower you breathe, less airflow resistance
•
Increases in obstructive and restrictive disease
•
Faster you breathe, less elastic resistance
•
Different patterns Obstructive
Restrictive Total Normal
Air Flow
Elastic 15
15
Breaths per minute
Breaths per minute
39
Obstructive Lung Diseases
Obstructive Lung Disease
•
Key points: Air trapping, slow flow out, less air out
•
Reduced FEV1 (slow flow out)
•
Reduced FEV1/FVC (hallmark)
Jason Ryan, MD, MPH
Residual & Total Lung Volume •
Both go up in obstructive disease •
•
Obstructive Lung Diseases •
From air trapping
Both fall in restrictive disease •
Less air fills the lungs due to restriction
Chronic Bronchitis •
Chronic cough Productive of sputum
•
At least 3 months over two years
•
•
•
Chronic bronchitis
•
Emphysema Asthma
•
Bronchiectasis
•
Chronic Bronchitis •
•
No other cause of cough present Strongly associated with smoking
40
Hypertrophy of mucous secreting glands Reid Index •
Thickness of glands/total wall
•
>50% in chronic bronchitis
•
Lungs can plug with mucous“mucous plugging”
•
Increased risk of infection
Chronic Bronchitis •
Poor ventilation of lungs
•
Increased CO2 Decreased O2
•
Hypoxic vasoconstriction
•
•
•
Chronic Bronchitis •
Pulmonary hypertension Right heart failure (cor pulmonale)
Shunting
Cough
•
Wheezing Crackles
•
Dyspnea
•
Cyanosis (shunting)
•
Emphysema •
•
Smokers •
Too many proteases created
•
Overwhelm anti-proteases
•
Upper lung damage
α1 anti-trypsin deficiency •
•
Ineffective anti-proteases Lower lobe damage Proteases
Anti-Proteases 99%
<99% O2 < 99%
Emphysema •
•
•
•
Emphysema
Destruction of alveoli •
Smoke activates macrophages
•
Recruitment of neutrophils
•
Release of proteases
•
Dyspnea Cough (less sputum than chronic bronchitis)
•
Hyperventilation
•
•
Loss of elastic recoil Small airways collapse on exhalation Air “trapped” in lungs
•
•
41
Weightloss Cor pulmonale Barrel Chest
Acinus •
Acinus = bronchiole + alveoli
•
Smokers = centriacinar damage
•
α1 anti-trypsin deficiency = panacinar
Chest Volumes and Pressures Chest Wall Lungs
FRC
System -40
Blue Bloater – Pink Puffer •
•
Chronic Bronchitis– Blue Bloater •
Cyanosis from shunting (blue)
•
Air trapping (bloated)
Emphysema – Pink Puffer •
•
Loss of alveoli
•
Loss of surface area for O2 absorption Hyperventilation to compensate (puffer)
•
Initially this maintains O2 level (pink)
•
•
•
Inherited (autosomal co-dominant)
20
40
COPD •
Chronic Obstructive Pulmonary Disease
•
Includes chronic bronchitis, emphysema, asthma Many similar symptoms (cough, dyspnea, wheezing)
•
Many similar treatments
•
1 Anti-trypsin Deficiency •
0
-20
1 Anti-trypsin Deficiency •
Decreased or dysfunctional AAT AAT balancesnaturally occurring proteases
Lung •
•
Elastase found in neutrophils & alveolar macrophages
•
•
Imbalance between neutrophil elastase (destroys elastin) and elastase inhibitor AAT (protects elastin) Lower lung damage
Livercirrhosis •
•
•
42
Panacinar emphysema
Abnormal
1 builds up inliver
Only occurs in phenotypes with pathologic polymerization of AAT in endoplasmic reticulum of hepatocytes Some patients have severe AAT deficiency but no intrahepatocytic accumulation
1 Anti-trypsin Deficiency •
Asthma
Classic case •
Typical COPD symptoms: cough, sputum, wheeze
•
Younger patient (40s)
•
Imaging: emphysematous changes most prominent at bases
•
Obstructive PFTs
•
Question often asks about panacinar involvement
•
These patients should NEVER smoke •
•
•
•
•
Cold
•
Aspirin
•
Rhinitis, eczema
•
May have family history of allergic reactions
Aspirin Exacerbated Respiratory Disease •
•
•
•
Asthma, chronic rhinosinusitis, nasal polyposis •
Chronic asthma/rhinosinusitis symptoms
•
Acute exacerbations after ingestion aspirin or NSAIDs
Dysregulation of arachidonic acid metabolism Overproduction leukotrienes Treatment: Leukotriene receptor antagonists •
Asthma Symptoms •
Episodic symptoms Dyspnea, wheezing, cough
•
Hypoxia during episodes
•
•
•
Decreased I/E ratio Reduced peakflow Mucous plugging (airway obstruction/shunt)
•
Death: Status asthmaticus
•
Type I hypersensitivity reaction
Airways are HYPERresponsive Common in children Associated with other allergic (atopic) conditions
AERD
URI
•
•
Usually due to allergic stimulus
Stimulates neutrophil elastase production
Allergens (animal dander, dust mites, mold, pollens) Stress Exercise
•
Reversible bronchoconstriction
•
•
Asthma Triggers •
•
Montelukast, Zafirlukast
Asthma Diagnosis •
•
43
Usually classic history/physical exam Methacholine challenge •
Muscarinic agonist
•
Causes bronchoconstriction
•
Administer increasing amounts of nebulized drug
•
Spirometry after each dose
•
Look for dose at which FEV1 falls significantly
•
If dose is low positive test
Asthma Pathology •
Recurrent episodes
•
Smoothmusclehypertrophy
•
Inflammation
Asthma Pathology •
Pulsus Paradoxus •
Most frequent non-cardiac causes are asthma/COPD
•
•
Bronchiectasis Symptoms •
Recurrent infections Cough, excessive sputum (foul smelling)
•
Hemoptysis
•
•
•
Curschmann’s spirals
•
Charcot-Leyden crystals
Bronchiectasis •
•
Classic sputum findings
Result of chronic, recurrent airway inflammation Airways become permanently dilated Obstruction •
Large airways dilated
•
Small/medium airways thickened bronchial walls
Bronchiectasis Etiologies •
Obstruction (tumor) Smoking
•
Cysticfibrosis
•
•
Cor pulmonale Amyloidosis
•
44
Kartagener’s syndrome Allergic bronchopulmonary aspergillosis
Primary Ciliary Dyskinesia
Kartagener’s syndrome
Immotile-cilia syndrome •
Cilia unable to beat, beat normally, or absent
•
Inherited (autosomal recessive) Gene mutations dynein structure/formation
•
Dynein = motor protein creates movement
•
•
•
Child
•
Recurrent sinus/ear infections
•
Chronic cough
•
Bronchiectasis on chest CT
•
Obstruction on PFTs
•
Situs inversus
Question often asks about dynein protein
ABPA
Situsinversus
•
Hypersensitivity (allergic) reaction to aspergillus
•
Lungs become colonized with Aspergillus fumigatus •
Low virulence fungus
•
Only infects immunocompromised or debilitated lungs
•
Occurs predominantly in asthma and CF patients
•
ABPA patients: •
Increases Th2 CD4+ cells
•
Synthesis interleukins
•
Eosinophilia
•
IgE antibody production
Summary
Allergic bronchopulmonary aspergillosis •
•
Allergic bronchopulmonary aspergillosis
Classic case: •
Bronchiectasis (chronic cough, recurrent infections) Male infertility
ABPA
Kartagener’s syndrome •
Chronicsinusitis
•
•
Lung Diseases
Classic case •
Asthma or CF patient
•
Recurrent episodes cough, fever,malaise
•
Brownish mucus plugs, hemoptysis
•
Peripheral blood eosinophilia High IgE level
•
Bronchiectasis on imaging
•
PFTs with obstruction
•
•
Diagnosis: Skin testing aspergillosis
•
Treatment: Steroids
Restrictive
Obstructive Bronchiectasis
Chronic Bronchitis
Asthma Emphysema Obstruction Smoking
Smoking α1-antitrypsin
45
Cystic Fibrosis Kartagener’s ABPA
Restrictive Lung Diseases
Restrictive Lung Disease
•
Key points:Can’t get air in less air out
•
Reduced FVC (less air in/out)
•
Normal (>80%) FEV1/FVC (hallmark)
Jason Ryan, MD, MPH
Causes
Poor Breathing Mechanics
•
#1: Poor breathing mechanics
•
•
#2: Interstitial lung diseases
•
•
•
Not a primary pulmonary issue Under-ventilation of lungs Alveoli working: A-a gradient normal Neuromuscular •
•
ALS, Polio, myasthenia gravis
Structural •
Scoliosis
•
Morbid obesity
DLCO
Interstitial Lung Disease
Diffusing capacity in lung of carbon monoxide
•
DLCO separates cases restrictive disease Restriction with normal DLCO
•
Restriction with low DLCO
•
•
•
Bilateral, diffuse pattern Small, irregular opacities (reticulonodular) “Honeycomb” lungappearance.
46
Extra-pulmonary cause: obesity
Interstitial lung disease
DLCO •
DLCO = diffusing capacity of carbon monoxide
•
Measures ability of lungs to transfer gas to RBCs Patient inhales small amount (not dangerous) CO
•
CO uptake is diffusion limited
•
•
•
•
•
Low DLCO Conditions •
•
•
•
Prior lung resection
•
Anemia
Normal = 75 – 140% predicted Severe disease <40% predicted
•
Pulmonary hypertension
•
Pulmonary embolism
•
Interstitial Diseases •
Emphysema Abnormal vasculature
Amount taken up ≈ diffusion functionlungs
Machine measures CO exhaled
Interstitial lung disease
•
•
Interstitial Diseases
“Diffuse parenchymal lungdiseases” Large group of disorders Similar clinical, radiographic, physiologic, or pathologic manifestations
•
Idiopathic pulmonary fibrosis
•
Systemic diseases with interstitial lung features •
Scleroderma
•
Rheumatoid arthritis
•
Goodpasture’s
•
•
•
•
Hypersensitivity pneumonitis
Pneumoconiosis
Idiopathic pulmonary fibrosis •
Most common type: Idiopathic interstitial pneumonia Slow onset dyspnea
•
Typically affects adults over the age of 40
Wegener’s Sarcoidosis
Pneumoconiosis Drug toxicity (amiodarone, methotrexate)
•
•
Corrects when adjusted for Hb level
Occupational lung diseases •
•
•
47
Coal miner’s lung Silicosis Asbestosis
Coal miner’s lung
Silicosis
•
Inhalation of coal dust particles
•
•
CXR or Chest CT:
•
•
Small, rounded, nodular opacities
•
Preference for the upper lobes
Silicosis •
•
•
High prevalence of bronchogenic carcinoma
•
•
Inhalation of asbestos fibers Shipbuilding, roofing, plumbing
•
Classically affects lower lobes
•
Most widespread pneumoconiosis in US Foundries (metal production facilities)
•
Sandblasting (abrasive blasting)
•
Mines
•
Affects upper lobes
•
Eggshell calcifications of lymph nodes
Impaired macrophage killing
Asbestosis •
•
Silicosis
Macrophages react to silica Inflammation fibroblasts collagen High prevalence of TB
•
Inhalation of silica in quartz, granite, or sandstone
Asbestosis •
•
•
Three clinical problems: •
Interstitial lung disease (asbestosis)
•
Pleural plaques
•
Lung cancer
CXR: Calcified pleural plaques pathognomonic Path: Asbestos bodies (ferruginous body)
48
Asbestos fibers surrounded by a coating of iron and protein
Asbestosis
Drug toxicity
•
Bronchogenic carcinoma
•
•
Mesothelioma
•
•
Asbestos is the only known risk factor for mesothelioma
•
Occurs decades after exposure
•
Pleural thickening and pleural effusion
•
Slow onset symptoms (dyspnea, cough, chest pain)
•
Poor prognosis
Hypersensitivity pneumonitis •
•
•
•
Busulfan Amiodarone
•
Methotrexate
Hypersensitivity pneumonitis
Hypersensitivity reaction to environmental antigen
•
Classic case
•
Agricultural dusts
•
Farmer or bird handler
•
Microorganisms (fungal, bacterial, or protozoa)
•
Cough, dyspnea, chest tightness
•
Chemicals
•
Diffuse crackles
Mixed type III/IV hypersensitivity
•
Moldy hay, grain exposure
Also common in bird/poultry handlers •
Diagnosis (challenging): •
Classic case is afarmer’s lung •
•
Bleomycin
•
Waste from birds dried, finely dispersed dust
49
•
Bronchoalveolar lavage Inhalation challenge
•
Lung biopsy
Treatment: •
Avoid exposure
•
Steroids
COPD and Asthma Drugs
Treatment of COPD & Asthma
•
Short-acting bronchodilators
•
Long-acting bronchodilators
•
Albuterol
•
Ipratropium
•
•
Salmeterol, Formoterol
Steroids
Jason Ryan, MD, MPH
2 Agonists •
•
•
Muscarinic Antagonists
Activateadenylatecyclase ↑cAMP Relax bronchiole smooth muscle Short acting: Albuterol
•
Vagal nerve Ach Bronchoconstriction
•
MA drugs block M receptors smooth muscle
•
Prevents bronchoconstriction
• Nebulizer or inhaler • Use during acute attacks (prn) •
Long acting: Salmeterol, Formoterol
•
Systemic side effects (rare)
• Not used as monotherapy (always with ICS)
• Hypertension, arrhythmia
Muscarinic Antagonists •
•
Steroids
Short acting: Ipratropium Long acting: Tiotropium
•
•
•
50
Inhaled: Beclomethasone, Fluticasone, Budesonide Oral: Prednisone IV: Methylprednisolone (Solumedrol)
Steroids •
•
•
•
•
Steroids
Inhibit synthesis of cytokines Bind to glucocorticoid receptor (GR) Many,many immunosuppressive effects
•
Common side effect is oral candidiasis(“thrush”)
•
Patients instructed to rinse after inhalation
↓ expression many interleukins, IFNγ, TNF-α, GM-CSF Inactivation NF-KB •
Transcription factor
•
Induces production of TNF- α
Special Asthma Drugs •
•
Eicosanoids Zileuton
Leukotriene receptor antagonists (PO) •
Montelukast (Singulair)
•
Useful in aspirin sensitive asthma
Lipids (cell membranes) Phospholipase A2
Arachidonic acid
Zileuton (PO) •
•
Lipoxygenase
5-lipoxygenase inhibitors Blocks conversion of arachidonic acid to leukotrienes
yclooxygenase
eukotrienes Thromboxanes Prostaglandins
Montelukast LTD4
Special Asthma Drugs •
•
Theophylline
Omalizumab (SQ injection) •
IgG monoclonal antibody
•
Inhibits IgE binding to IgE receptor on mast cells & basophils
•
Methylxanthines Multiple, complex mechanisms
•
Bronchodilation
•
Cromolyn (inhaler/nebulizer) •
Inhibits mast cell degranulation
•
Blocks release of histamine, leukotrienes •
51
•
Likely through inhibition PDE
•
Less hydrolysis (br eakdown) cAMP
•
↑cAMP
Also down-regulates inflammatory cell functions
Theophylline •
Theophylline
Narrow therapeutic index
•
•
Levels must be monitored Dose must be titrated
•
Goal is a peak serum concentration 10 to20mg/L
•
•
•
Metabolized by P450 Many drug-drug interactions Common culprits: •
Cimetidine
•
Ciprofloxacin
•
Erythromycin
•
Clarithromycin
•
•
Theophylline •
•
•
Nausea, vomiting
Neurotoxicity •
•
Theophylline
GI toxicity •
Verapamil St. John’s Wart
Seizures
Overdose scenario: Nausea, vomiting, seizures •
Cardiotoxicity •
Blocks adenosine receptors
•
Increased heart rate
•
Arrhythmias (atrial tachycardia, atrial flutter)
•
Cause of death in overdose/poisoning
Key clinical scenario for asthma/COPD Patient on theophylline •
Steroids Zileuton Cromolyn
Avoidance of Triggers
•
•
X
Omalizumab
SVT
•
Adenosine fails to slow heart rate
Special COPD Drugs
Asthma
Antigen
•
X
Mast Cell
X
IgE
Leukotrienes Histamine IgE
Broncho Constriction X
agonists M antagonists Theophylline LRAs
52
Theophylline Roflumilast (PO) •
Phosphodiesterase-4 (PDE-4) inhibitor
•
Decreases inflammation
•
May relax airway smooth muscle
Treatment Asthma & COPD
COPD: Acute Exacerbations •
Asthma
Acute Exacerbations
COPD
Chronic Therapy
Acute Exacerbations
Chronic Therapy
GOLD Criteria
COPD: Chronic Therapy
•
Associated with increased survival
•
PaO2 < 55mmHG or O2 sat <88%
•
Antibiotics (severe, hospitalized patients)
Improves exercise capacity, quality of life
•
Decrease dyspnea
•
Vaccinations
•
Smoking cessation
Prednisone 60mg daily
•
Methylprednisolone 80mg IV q8hrs
•
Fluoroquinolones
•
Amoxicillin/clavulanate
•
Oxygen Nebulizedalbuterol
•
IV or oral corticosteroids
•
Pulmonary rehabilitation •
•
Asthma: Acute Exacerbations
Oxygen •
Nebulized albuterol +/- ipratropium (Combivent) IV or oral corticosteroids
COPD: Chronic Therapy
Global Initiative for Chronic Obstructive Lung Disease
•
Oxygen
•
•
•
53
•
Prednisone 60mg daily
•
Methylprednisolone 80mg IV q8hrs
Rarely used: •
Ipratropium
•
IV Magnesium sulfate
Asthma: Chronic Therapy
Step 1 SABA as
Step 2 Add Low dose ICS
Step 3 Medium ICS or Low ICC + LABA
Step 4 Medium ICS + LABA
Step 5 High ICS + LABA
Surgical Treatment
Step 6 High ICS + LABA + Oral Steroids
•
For advanced“end-staged” COPD
•
Lung volume reduction surgery/Bullectomy
•
needed LTRA, Zileuton, Theophylline, Omalizumab
54
•
Remove diseased lung tissue
•
Allow healthy lung tissue more room to expand
Lung transplant
Pneumonia •
Infection of the lungs
•
Three patterns •
Lobar
•
Bronchopneumonia
•
Interstitial (atypical)
Pneumonia Jason Ryan, MD, MPH
Lobar Pneumonia •
Classic form of pneumonia S( . pneumoniae)
•
Bacteria acquired in nasopharynx Aerosolized to alveolus Enter alveolar type II cells
•
Pneumococci multiply in alveolus
•
•
•
Invade alveolar epithelium Pass from one alveolus to next (pores of Cohn)
•
Inflammation/consolidation oflobes
•
Can involve entire lung
•
Four Lobar Stages
•
Gray, f irm lobe
•
Exudate with neutrophils/fibrin
•
RBCs disintegrate
•
Dying pneumococci Return to normal (little scarring)
•
Enzymes digests exudate
•
Type II pneumocyte key for regeneration
#2: Red hepatization (2-3days)
•
Alveolar capillaries dilate
•
Exudate of bacteria develops Exudate of RBCs, neutrophils, fibrin
•
“Fresh" exudate: RBCs/WBCsintact Pneumococci alive
•
Lobes look red
Bronchopneumonia •
•
•
#4: Resolution •
•
•
#3: Gray hepatization (4-6days) •
#1: Congestion (1st 24 hours)
•
Four Lobar Stages •
•
55
Patchy inflammation of multiple lobules Primary involvement airways and surrounding interstitium Staphylococcus aureus
Interstitial Pneumonia •
•
•
•
•
•
Atypical Pneumonia
Inflammatory infiltrate of alveolar walls only
•
More indolent course Viruses Legionella pneumophila
•
Mycoplasma pneumoniae Chlamydophila pneumoniae
•
•
•
Pneumonia caused by: •
Legionella pneumophila
•
Mycoplasma pneumoniae
•
Chlamydophila pneumoniae
Usually milder than strep pneumonia Respiratorydistressrare Interstitial infiltrates on CXR “Walking pneumonia”
Causes of Pneumonia
Causes of Pneumonia
Children
Adults •
•
•
Legionella
•
Causes of Pneumonia
Signs/Symptoms
Adults •
•
•
•
Gram-negative rods •
Klebsiella, E. Coli, Pseudomonas
•
Uncommon unless severe PNA
•
Often isolated in hospitalized patients
•
•
•
•
S. Aureus (postinfluenza pneumonia) Anaerobes (aspiration PNA; lung abscess) Viruses •
Influenza
•
RSV (children)
S. pneumoniae– most common Haemophilus influenzae Mycoplasma pneumoniae C. pneumoniae
•
•
56
High Fever Cough Sputum production Elevated WBC Pleuritic chest pain
Diagnosis •
•
Clinical Classes of Pneumonia
Usually: •
History
•
Physical exam
•
X-ray (sometimes CT scan)
•
Community acquired
•
Nosocomial
Rarely
•
Usually S. Pneumoniae, H. Influenza, S. Aureus
•
Sometimes Mycoplasma, Chlamydia, Legionella(atypicals)
•
Bad bugs
•
Sputum culture
•
Often gram negatives (Pseudomonas, Klebsiella, E. Coli)
•
Bronchoalveolar lavage
•
Hospital Acquired
• •
Ventilator-associated pneumonia (VAP) Healthcare-associated pneumonia (HCAP; nursing homes)
Community Acquired PNA
Community Acquired PNA
Uncomplicated
Complicated
•
•
•
•
•
No co-morbidities
•
No recent antibiotic use Low community rates resistance Azithromycin, Clarithromycin, or Doxycycline Three to five day course •
COPD, CKD, Diabetes, CHF, Alcoholism
•
Recent antibiotic use Fluoroquinolone (levofloxacin)
•
Amoxicillin plus azithromycin
•
Patient should be afebrile 48-72 hrs and clinically stable
Complications
Nosocomial PNA •
Lots of resistance to antibiotics
•
•
Gram negative rods
•
Sepsis Respiratory failure
•
Lungabscesses
•
•
•
E. coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter
Staph Aureus including MRSA Often cover for pseudomonas, MRSA
•
Sometimes multi-drug combinations Cefepime or Ceftazidime
•
Imipenem or Meropenem
•
Piperacillin-tazobactam (Zosyn)
•
•
•
57
Pleural effusion ARDS
ARDS
ARDS
Acute Respiratory Distress Syndrome
Triggers
•
Triggered by various lung injuries
•
•
Injury release of pro-inflammatory cytokines
•
•
•
•
TNF, interleukins
•
•
•
Fluid pours into the interstitium
Legionella
Treatment Mechanical ventilation
•
Low tidal volume Supportive care(fluids, nutrition)
•
VAP pneumonia is serious complication
•
Transfusion-related acute lung injury (TRALI)
ARDS •
•
•
Reactive oxygen species, proteases
Damage to capillary endothelium and alveolar epithelium Protein escapes from vascular space
•
•
Infection (PNA) Aspiration Trauma Acute pancreatitis
•
Cytokines recruit neutrophils to lungs Neutrophils release toxic mediators
Sepsis (most common)
•
First identified at American Legion convention
•
Infection from inhalation of aerosolized bacteria
•
Outbreaks at hotels with contaminated water
•
Can cause nosocomial pneumonia in nursing homes
•
Not airborne
Legionella
Legionella
Symptoms
Diagnosis
•
Initially mild pneumonia symptoms •
•
•
•
•
Urinary antigen test
•
Watery diarrhea, nausea, vomiting, and abdominal pain Can occur in any PNA but more common Legionella
58
Does not gram stain well
Buffered charcoal yeast extract agar (BCYE) Iron and cysteine added for growth Supplemented with antibiotics and silver dyes
•
Hyponatremia (Na<130 meq/L) common •
Special culture requirements •
Can progress to severe pneumonia GI symptoms •
•
•
Fever; mild, slightly productive cough
•
Antimicrobials prevent overgrowth by competing organisms
•
Dyes give distinctive color to Legionella
•
Rapid test available in minutes
•
Does not test for all Legionella types
Legionella
Pontiac Fever
Diagnosis •
•
•
Classic Case
•
•
Mild cough
•
Watery diarrhea
•
Confusion (low Na)
•
Negative bacteria on gram stain
•
Atypical pneumonia Can’t see on gram stain (no cell wall)
•
Classically causes outbreaks in young adults
• •
•
•
•
Chestradiographusually normal
•
College dorm residents
•
Military recruits
Influenza Virus •
•
•
Major complication is secondary pneumonia
•
CXR looks worse than symptoms Can cause autoimmune hemolytic anemia
•
IgM antibody
•
“Cold” hemolytic anemia
Atypical pneumonia Influenza A or B viruses Fever, headache, myalgia, andmalaise Nonproductive cough, sore throat, runny nose
•
RBC antigen
•
Strep pneumoniae, Staph aureus, H. influenzae
•
Worsening symptoms after initial improvement
•
Cause of death
Stevens-Johnson syndrome
RSV
CMV •
Fever, malaise, chills,fatigue, and headache No respiratorycomplaints
Diagnose with urinary antigen test Treatment: Fluoroquinolone or Azithromycin
Mycoplasma Pneumonia •
Mild form of Legionella infection
•
•
Respiratory Syncytial Virus
Pneumonia in transplant patients on immunosuppressive drugs
•
•
“Owl eye” intranuclear inclusions
•
Viral respiratory infection in infants Often seasonal outbreaks (Nov– April) Most common cause lower respiratory tract illness in children •
•
•
•
Runny nose
Few days later, lower tract symptoms •
59
Bronchiolitis, pneumonia, acute respiratory failure
Often starts as upper airway infection
Wheezing often present
RSV
RSV
Respiratory Syncytial Virus
Respiratory Syncytial Virus
•
Treatment: Ribavirin •
•
•
Inhibits synthesis of guanine nucleotides
Prevention: Palivizumab •
Monoclonal antibody against F protein
•
RSV contains surface F (fusion) protein
•
Causes respiratory epithelial cell fusion
•
Used in pre-term infants (high risk RSV)
•
Sometimes congenital heart disease
Aspiration Pneumonia •
•
•
•
Bugs from oral cavity and nasopharynx to lungs Risk factors:
•
•
•
•
•
Fever, runny nose
•
Few days later, cough, wheezing
Klebsiella Staph Aureus Anaerobic bacteria
Reduced consciousness (anesthesia)
•
Peptostreptococcus
•
Seizures
•
Fusobacterium
•
Alcoholics Dysphagia from neuromuscular weakness
•
Classic patients: •
Debilitated nursing home patient
•
Alcoholic
•
Klebsiella Pneumonia •
Young child (often <2yo)
•
•
•
•
•
Aspiration Pneumonia
Aspiration of microorganisms
•
•
Classic case
Prevotella Bacteroides
Clindamycin first-line therapy
Lung Abscess
Can cause lobar pneumonia Often from aspiration Marked inflammation/necrosis
•
Contained, fluid-filled space in lungs
•
Usually a consequence of aspiration
•
•
Thick, mucoid and blood-tinged sputum “Currant jelly"
•
60
“Air fluid level” on imaging
Rarely due to bronchial obstruction from cancer Predominantly anaerobes •
Peptostreptococcus
•
Prevotella
•
Bacteroides
•
Fusobacterium
•
Sometimes S. Aureus, Klebsiella
•
Treatment: Clindamycin
PCP
PCP
Pneumocystis jirovecii
Pneumocystis jirovecii
•
Diffuse interstitial pneumonia
•
Requires immunocompromise
•
•
Classically HIV
•
AIDS-defining illness
Pneumocystis jirovecii
•
Treatments •
TMP-SMX (first line)
•
Dapsone
•
Pentamidine
Prophylaxis •
•
•
Staining required cannot be cultured
•
Special stains used •
Usually no symptoms if immune system intact
PCP •
Diagnosed by microscopy •
Yeast inhaled •
•
TMP-SMX when CD4 <200cells/microL High dose steroid or other immunosuppressant
61
Sputum sample or BAL
Silver stains often used
What are the pleura? •
•
Visceral pleura – attached to lung
•
Parietal pleura – attached to chest wall
•
Pleural space/cavity– between layers Pleural lined by mesothelial cells
•
Secrete small amount pleural fluid for lubrication
•
Pleural Disease
Two layers of tissue surrounding lungs
Jason Ryan, MD, MPH
Pneumothorax •
Air in pleural space
•
Two types to know about •
Spontaneous
•
Tension
Spontaneous PTX •
Primary
•
Secondary
•
Rupture of subpleural bleb
•
Common in tall, thin young males
•
•
•
Sudden onset dyspnea Sometimes pleuritic chest pain
•
CXR for diagnosis
COPD
Pneumothorax
Spontaneous PTX •
Older patients with underlying pulmonary disease
Treatment •
•
100% Oxygen •
Displaces nitrogen from capillary blood
•
↑gradient for nitrogen reabsorption from pleural space
Chest tube •
62
Larger pneumothoraces (>15% lung volume)
Tension PTX •
Usually from trauma
•
Air enters pleural space but cannot leave Medical emergency
•
Emergent thoracentesis/chest tube placement
•
Trachea deviatesAWAY from affected side
•
Pleural Effusion •
Pleural Effusion •
Transudative Effusion
Three general etiologies •
Transudative
•
Exudative
•
Lymphatic
•
•
•
•
Exudative Effusion •
•
•
•
•
•
Something driving fluid into pleural space Most commonly due to CHF (High pressure) Other causes: •
Nephrotic syndrome (low protein)
•
Cirrhosis (low albumin)
•
Mostly fluid in effusion Very little protein in effusion
•
Usually treat for underlying cause (no drainage)
Transudate vs. Exudate
Fluid leaking into pleural space •
Accumulation of fluid in pleural space
•
High vascular permeability
•
Many causes
•
Malignancy Pneumonia More protein in pleural fluid vs. transudative Usually requires drainage
63
Thoracentesis to obtain fluid sample Test for protein, LDH Light’sCriteria – Exudate if: •
Pleural protein/serum protein greater than 0.5
•
Pleural LDH/serum LDH greater than 0.6
•
Pleural LDH greater than 2/3 upper limits normal LDH
Lymphatic Effusions
Other Effusions
“Chylothorax” •
Lymphatic fluid effusion
•
From thoracic duct obstruction/injury Malignancy most common cause Trauma (usually surgical) Milky-appearing fluid
•
Very high triglycerides
•
•
•
•
Pleural tumor Asbestos is only known risk factor •
•
•
•
Decades after exposure
Poor prognosis Median survival 4 to 13 months untreated
•
6 to 18 months treated with chemo
Empyema
64
High Hct in fluid
•
Infected pleural fluid
•
Pus, putrid odor, positive culture
Malignant effusion •
Imaging: Pleural thickening and pleural effusion Slow onset symptoms (dyspnea, cough, chest pain) •
•
•
Mesothelioma •
Hemothorax •
TG usually > 110 mg/dL
•
•
Positive cytology
Common Cancers •
Breast
•
Prostate Lung (most deadly)
•
Colorectal
•
Lung Cancer Jason Ryan, MD, MPH
Lung Cancer Risk Factors •
Cigarette smoking •
•
Polycyclic Aromatic Hydrocarbons (PAHs)
Radiation Therapy •
•
Symptoms
•
Cough, dyspnea, rarely hemoptysis
•
Usually leads to chest imaging
Hodgkin's and breast cancer survivors
Asbestos Radon
Diagnosis •
Pulmonary nodule “Coin lesion”
•
Compare with prior
•
Usually advanced at presentation
•
Environmental toxins •
•
•
Benign Pulmonary Nodules •
•
Granulomas (80% benign nodules) Hamartomas •
Biopsy for diagnosis
65
Lung tissue and cartilage (with scattered calcification)
Granulomas •
•
Lung Cancers
Fungi
•
Small cell (15%)
•
Histoplasmosis (patient from Midwest, Miss/Ohio river valley)
•
Fast growing; Early mets
•
Coccidioidomycosis (southwest, California)
•
Non amenable to surgical resection
•
Smokers
•
Treated with chemo
•
Poor prognosis
Mycobacteria •
Usually tuberculosis •
Non-small cell (Most Common: 85%) •
Can sometimes be resected Better prognosis
•
Smokers and non-smokers
•
Small Cell Cancer
Small Cell Cancer •
•
Paraneoplastic Syndromes
Poorly differentiated small cells Classic in male smokers
•
Neuroendocrine tumor
•
Central tumor
•
•
ACTH •
Cushing syndrome
•
Progressive obesity
•
Hyperglycemia
ADH •
•
•
Non-Small Cell Cancers •
Squamous Cell Carcinoma Adenocarcinoma
•
Large cell carcinoma
•
•
•
SIADH Hyponatremia (confusion)
Antibodies •
Antibodies against pre-synaptic Ca channels in neurons
•
Block release of acetylcholine
•
Lambert-Eaton syndrome
•
Main symptom is weakness
Squamous Cell Carcinoma •
•
Bronchioloalveolar Carcinoma Carcinoid tumor
•
•
66
Hilar mass arising from bronchus Key pathology •
Keratin production (“pearls”) by tumorcells
•
Intercellular desmosomes ("intercellular bridges")
Male smokers Can produce PTHrP •
Hypercalcemia
•
Stones, bones, groans, psychiatric overtones
•
Bone and abdominal pain, confusion
Adenocarcinoma •
Glandulartumor
•
Most common lung cancer: nonsmokers/females
•
Peripheral
Large Cell Carcinoma •
Poor prognosis
Carcinoid tumor
Subtype of adenocarcinoma
•
Many similar features to adeno:
•
•
•
•
Nonsmokers, Peripheral
Rarely causes carcinoid syndrome •
Secretion of serotonin
•
Flushing, diarrhea
Excellent prognosis Surgery, radiotherapy, sometimes adjuvant chemotherapy
SVC Syndrome
Pleuraleffusions •
•
•
Lobar consolidation
Complications
•
•
Looks like PNA on CXR
•
•
Neuroendocrine Well-differentiated cells Chromogranin positive Non-smokers
•
Mucinous type: Derived from goblet cells Nonmucinous: Clara cells or type II pneumocytes •
Lacks small cells
•
•
•
Lacks glandular or squamous differentiation
•
•
•
•
•
Smokers cancer Central or peripheral
•
Bronchioloalveolar Carcinoma
Poorly differentiated
•
Tap fluid, send for cytology
•
Phrenic nerve compression •
Diaphragm paralysis
•
Dyspnea
•
Hemidiaphragm elevated on CXR
•
Sniff test
•
•
Lung Masses: NSCLC, SCLC
•
Mediastinal Masses: Lymphoma
Other causes include thrombosis •
•
Recurrent laryngeal nerve compression •
Obstruction of blood flow through SVC Can be caused by compression from tumor
•
Hoarseness
•
67
Indwelling catheters, pacemaker wires
Facial swelling or head fullness Arm swelling Can cause increased ICP •
Headaches, confusion, coma
•
Cranial artery rupture
SVC Syndrome
Pancoast Tumor
•
Usually diagnosed CXR or CT Chest
•
Carcinoma at apex of lung
•
Various treatment options:
•
Involvesuperior sulcus
•
Anticoagulation f or thrombus
•
Steroids (lymphoma)
•
Chemo/Radiation
•
Endovascular stenting
•
•
•
•
•
•
Metastasis from Lung Cancer •
•
Usually found on imaging without symptoms
Brain •
Headache, neuro deficits, seizures
•
Bone
•
Liver
•
•
Can compress sympathetic nerves Horner's syndrome •
Miosis
•
Ptosis
•
Anhidrosis
Metastasis to Lung
Adrenals •
Groove formed by subclavian vessels
Arm edema affected side Shoulder pain radiating toward axilla/scapula Arm paresthesias, weakness
Pathologic fractures Hepatomegaly, jaundice
68
•
More common than primary lung tumors
•
Most commonly from breast or colon cancer
•
Usually multiple lesions on imaging
Sleep Apnea •
Apnea = cessation of breathing
•
Sleep apnea = cessation of breathing during sleep Usually >10 seconds
•
Multiple episodes per night are typical
•
Sleep Apnea Jason Ryan, MD, MPH
Sleep Apnea Symptoms •
Unrestful sleep
•
Daytime somnolence
•
Loud snoring
Sleep Apnea Types •
Central sleep apnea
•
Obstructive sleep apnea
•
•
Central Sleep Apnea •
•
Cheyne-Stokes breathing
•
Hypoventilate when awake
•
•
Fall asleep apnea periods
•
•
Central nervous system disease (encephalitis)
•
•
Neuromuscular diseases (polio, ALS) Severe kyphoscoliosis
•
Narcotics
Decreased air flow despite effort to breathe
Central Sleep Apnea
Patients with marginal ventilation when awake
•
No effort to breathe
69
Cyclic breathing Delayed detection/response to changes in PaCO2 Common in heart failure and stroke patients
Obstructive Sleep Apnea
Sleep Apnea Complications
•
Recurrent soft tissue collapse in the pharynx
•
•
Strongest risk factor is obesity
•
Erythropoiesis
•
Pulmonary HTN Arrhythmias
•
Sudden death
Sleep Apnea Diagnosis
•
Chronic hypoxia
•
•
EPO release
•
Sleep Apnea Treatments Weight loss
•
CPAP
•
Upper airway surgery
•
•
•
Takes time; not best option for exhaustedpatients
First line for symptomatic patients Severe disease
70
Polysomnography “Sleep study”
•
Patient sleeps in monitored setting EEG, eye movements
•
O2 level, HR, respiratory rate
•
Number of apnea episodes recorded
•
•
HTN
Cystic Fibrosis •
•
•
Inherited genetic disease •
Autosomal recessive pattern
•
Both parents must be carriers
Results in thick, sticky mucus in lungs/GI tract Common cause chronic lung disease in children
Cystic Fibrosis Jason Ryan, MD, MPH
CFTR
CFTR
Cystic Fibrosis Transmembrane Regulator
Cystic Fibrosis Transmembrane Regulator
•
CFTR protein is abnormal in CF
•
ATP ion transporter
•
CFTR gene encodes for the abnormal protein
•
Epithelial Cell Functions •
Pumps Cl- out of epithelial cells
•
Against concentration gradient (uses ATP)
•
Creates a membrane potential that draws out Na/H2O
•
•
CFTR Mutations •
•
•
•
•
Removes NaCl from sweat (makes sweat hypotonic)
•
CF patients have high NaCl in sweat
CF Pathophysiology
Many mutations identified Most common mutation: delta F508 •
Hydrates mucosal surfaces (lungs, GI tract)
Sweat gland functions
•
Thick mucous in lungs •
Recurrent pulmonary infections (Pseudomonas, S. Aureus)
Deletion of 3 DNA bases
•
Chronic bronchitis
Codes for 508th AA acid: phenylalanine
•
Bronchiectasis
•
Most common consequence: abnormal processing
Thick mucous in GI tract
•
Abnormal protein folding
•
Impaired flow of bile and pancreatic secretions
•
Prevents protein trafficking to correct cellular location
•
Malabsorption especially fats
•
Loss of fat soluble vitamins (A, D, E, K)
•
Steatorrhea
71
CF Presentation •
Usually diagnosed<2yo
•
Respiratory disease (45%) Failure to thrive (28%)
•
Meconium ileus (20%)
•
CF Lung Disease •
Hyperinflation of lungs on CXR Obstructive pattern
•
Later disease
•
•
Pancreatic insufficiency •
•
•
•
•
CF-related diabetes Fat malabsorption Steatorrhea: Foul-smelling stools Oily or greasy
•
Stools may float
•
Deficiencies of fat-soluble vitamins: A, D, E, and K
•
Vitamin E: Ataxia, hemolysis
Other symptoms
Meconium
•
Biliary disease
•
Meconium: first stool of newborn
•
Bile duct obstruction
•
Very thick and sticky
•
Pale or clay colored stool
•
Elevation of LFTs
Meconium ileus = bowel obstruction •
Meconium too thick/sticky
•
•
Meconium plug forms
•
Hepatomegaly Cirrhosis
•
Gallstones
•
Abdominal distension Vomiting
•
Air fluid levels of X-ray
•
Failure to pass meconium
•
Bronchiectasis
Acute exacerbations Pseudomonas aeruginosa: major pathogen in CF
•
•
Meconium ileus •
Chronic bronchitis
•
Vitamin K: coagulopathy Vitamin D: rickets Vitamin A: Night blindness
•
Frequent stools
•
•
•
Pancreatic insufficiency
Chronic pancreatitis
•
Productive cough
•
•
72
Other symptoms •
Other symptoms
Infertility •
95 percent males with CF are infertile
•
Absent vas deferens
•
Problem is sperm transport not spermatogenesis
•
Can have children with assisted techniques
Diagnosis •
•
•
Small electrical current drives pilocarpine into skin
•
•
•
•
•
DNA testing done if sweat test abnormal
•
•
•
•
•
Inhaled DNase (dornase alfa)
•
Inhaled saline
•
N-acetylcysteine
Increased chloride ion flux
•
Only for patients with G551D mutation
Usually have milder disease
•
Often recurrent pulmonary and sinus infections
•
Measure nasal voltage CF patients: more negative voltage
•
Due to abnormal sodium processing
•
Pancreatic enzyme replacement Vitamins (A, D, E, K)
•
Vaccinations
•
Ivacaftor (tablets) •
•
If symptoms highly suggestive, can test nasal transepithelial potential difference
Other Treatments
Promote clearance of airway secretions •
Rare CF patients have negative sweat test
•
Treatment •
Nasal polyps
Sweating occurs Sweat collected on filter paper Chloride content analyzed High chloride level suggests CF
•
Digital clubbing
•
Diagnosis
Sweat chloride test Pilocarpine iontophoresis Pilocarpine gauze placed on skin Electrode placed over gauze
•
•
Exacerbations are treated with antibiotics Lung transplantation
73
Prognosis •
Average life span ~ 37 years
•
Death from lung complications
Screening
74
•
Prenatal
•
Newborn
•
Test for 23 most common CF mutations in US
•
Often test mother first and stop if negative
•
↑ blood levels immunoreactive trypsinogen (IRT)
•
Blood test if positive sweat test
Tuberculosis •
Ancient disease: Found in mummies!
•
Old name: Consumption Tubercle = round nodule
•
Tuberculosis = multiple round nodules
•
Tuberculosis Jason Ryan, MD, MPH
Mycobacterium tuberculosis •
•
Culture of TB
Obligate aerobes •
Prefer lungs
•
Reactivation disease prefers upper lobes
•
Facultative intracellular pathogens •
•
Infect macrophages
•
•
Difficult to culture •
Special media used
•
Lowenstein-Jensen agar
Slow growing Does not stain well with Gram stain This is due to mycolic acids in cell wall •
Acid Fast •
•
•
Virulence Factors
Cell walls impermeable to many dyes Stain with very concentrated dyes plus heat •
•
Lipid soluble; contain phenols
Once stained, plate rinsed with acid decolorizer •
•
“Acidfast stain”
•
TB resists decolorization with acid solvents
•
Some other bacteria (Nocardia) also do this
Also fatty acids and complex li pids
•
Trehalose dimycolate ("cord factor") •
Helps evade immune response
•
Causes granuloma formation
•
Triggers cytokine release
Sulfatides •
Glycolipids
•
Inhibits fusion of phagosomes/lysosomes
Catalase-peroxidase •
75
Resists host cell oxidation
Spread of TB •
Spreads through the air Active TBpatient’s cough, sneeze, etc.
•
Inhaled by uninfected person
•
Can spread rapidly in crowded areas
•
Exposure to TB •
Most patients will not develop active disease
•
Small proportion patients develop active disease
•
Infection can clear or remain “latent”
Primary TB
Primary TB
Clinical Picture
Pathophysiology
•
Mainly a disease of childhood or chemo patients •
•
•
•
•
•
•
Ineffective immune response
Gradual onset: weeks Fever Cough
•
TB infects macrophages
•
Phagocytosed
•
Intracellular bacterial proliferation
Pleuritic chest pain Fatigue, arthralgias
Primary TB
Granulomas
Pathophysiology •
First week
Two to four weeks •
Cell-mediated immune system controls TB
•
TH1 response
•
Activation of CD4+ T cells
•
•
•
Granulomatous inflammation Caseating necrosis
•
Macrophages transform to :
•
Interferon-γ secreted Activated macrophages and cytotoxic T lymphocytes
•
Epithelioid cells
•
Langhans giant cells
•
Fibroblasts activated collagen
•
T-cell mediated delayed type hypersensitivity reaction •
76
Type IV hypersensitivity reaction
Hilar Lymphadenopathy
Ghon Foci
CXR often normal Classic finding is hilar lymphadenopathy
•
•
Occur as early as 1 week after infection Resolveslowly over months to years
•
•
•
•
Disease heals leaving fibrosis
•
Sometimes completely clears
•
Usually enters latent phase (“walledoff”)
•
Immunity develops
•
PPD positive
•
•
•
Miliary dissemination
•
More common with HIV, CKD, DM (impaired immunity)
Miliary TB •
•
Spine infection (osteomyelitis)
•
Back pain, fever, night sweats, weight loss
Mid to lower lungs
Progressive primaryinfection or reactivation Nearly any organ system can be involved •
Bones
•
Liver
•
CNS (meningitis) Heart (pericarditis)
•
Skin
Reactivation TB
Pott’s disease •
Subpleural
•
Hematogenous spread of TB
•
Rare (10%) patients have expanded illness •
Granulomas
•
Miliary TB
Most (90%) patients control infection •
•
Ghon foci plus lymph node is Ghon complex Calcified Ghon complex is a Ranke complex
•
Primary TB Resolution •
Ghon foci form
•
•
Reactivation of dormant TB Cough, weight loss, fatigue
•
Fever
•
Constrictive pericarditis
•
•
Night sweats Chest pain Often cavitation (caseous and liquefactive necrosis)
•
Hemoptysis (erode pulmonary vasculature)
•
CXR classically shows upper lobe lesions
•
77
Reactivation TB •
Can occur when immune compromise develops
•
HIV infection TNF-α inhibitors
•
Diabetes
•
Aspergilloma •
•
Used in autoimmune diseases
•
Etanercept, Infliximab
Caused by Aspergillus fumigatus Non-invasive form of aspergillosis
•
Grows in pre-formed cavities
•
•
• •
•
TB Infection Summary
Infection Contained
Pulmonary TB is most common association Often asymptomatic Can cause hemoptysis Diagnosis: Imaging plus sputum culture Treatment: Observation vs. surgery
Diagnosis of Active TB •
Exposure
Infection Clears
Fungusball
•
•
Aspergillus ABPA Invasive Aspergillus Aspergilloma
Primary TB
•
Usual method: 3 sputum samples •
Usually about 8hrs apart
•
Spontaneous or induced
•
Induced: Inhalation of aerosolized saline by nebulizer
Acid-fast smear and culture
“Latent”
Reactivation TB
Milary TB
Diagnosis of Active TB •
Not necessary to hospitalize just for TB suspicion Outpatients: Remain at home, avoid visitors, mask
•
Inpatients: Respiratory isolation
•
•
Private room
•
Negative air pressure
•
Persons entering must wear a respirator
•
Tight seal over the nose and mouth
Diagnosis of Latent TB •
Identification of latent TB crucial to infection control Diagnosis: Tuberculin skin testing (TST)
•
SC injection purified protein derivative (PPD)
•
Wait 48 hours
•
Measure diameter of induration (not erythema)
•
•
78
5 tuberculin units (0.1 mL)
PPD Testing
PPD Testing •
False negatives can occur Immunosuppressive drugs
•
Immunocompromised
•
* Silicosis, CKD, DM, IV drug users, homeless, prison employees, others •
BCG Vaccine •
•
•
• •
•
Live strain ofMycobacterium bovis More effective in patients with no TB exposure About 80% effective in children
•
Less effective in adults
•
Isoniazid Rifampin
•
Pyrazinamide
•
Ethambutol
•
Sometimes streptomycin
•
Sometimes direct observation therapy (DOT)
•
Risk of Multi-drug resistant (MDR) TB
HIV
•
CKD
•
Malnutrition
Diseased lymph system •
Sarcoidosis
•
Some lymphomas or leukemias
Most patients with latent TB will not develop disease
•
Further PPD testing not indicated •
Will remain positive for life
Isoniazid
Requires multi-drug regimens Typical regimen: •
•
•
•
Used in children in areas with high prevalence of TB Creates false positive PPD
•
TNF- α inhibitors
Small proportion may reactivate Prophylaxislowersrisk Commonly isoniazid (INH) for 9 months
•
Treatment of Active TB •
Corticosteroids
•
Treatment of Positive PPD
Bacille Calmette-Guérin
•
•
•
•
•
79
Blocks synthesis of mycolic acids Bacteria lose their acid fastness katG-encoded catalase-peroxidase •
Converts INH to active form
•
Mutations lead to INH resistance
•
Monotherapy produces resistance
Isoniazid •
•
Neurotoxic •
Neuropathy, ataxia, and paresthesia
•
Competes with B6 as co-factor neurotransmitter synthesis
•
Pyridoxine (B6) co-administered
•
Limits neurotoxicity
•
Probably related to metabolites of INH
Blocks RNA synthesis Main side effects are liver, GI
•
Red/orange discoloration fluids (not dangerous)
Drug-induced lupus
Rifampin Leprosy
•
Meningococcal prophylaxis
•
Chemoprophylaxis in contacts of children HiB
•
Increased LFTs
•
GI upset: nausea, cramps, diarrhea
•
Urine
•
Saliva
•
Sweat, tears
•
CSF
Pyrazinamide
Other uses •
InhibitbacterialDNA-dependentRNA polymerase
•
•
Hepatotoxic (check LFTs) •
•
Rifampin
•
Mechanism unknown
•
Hepatotoxic
•
Converted to pyrazinoic acid (PZA)
•
May be more active in acidic environment inside macrophages
•
•
Ethambutol •
•
Red-green color blindness Difficulty discriminating red and green hues
•
Loss of visual acuity
•
Reversible
Hyperuricemia
•
Gout exacerbations
Older, aminoglycoside drug Inhibits bacterial 30S ribosomal subunit
•
Lots of resistance
Key side effect: optic neuropathy •
Can raise uric acid levels
•
•
•
Polymerizes arabinose for mycobacteria cell walls
•
•
Streptomycin
Inhibits arabinosyl transferase •
Can raise LFTs
Competes with uric acid for excretion in kidneys
•
•
80
Prevents protein synthesis Mutations of genes for ribosomal proteins
Tuberculosis Key Points •
Mycolic acid cell walls acid fast
•
Infects macrophages (intracellular) Delayed type hypersensitivity reaction
•
Hilar lymphadenopathy; Ghon complex
•
•
•
•
•
Reactivation in upper lobes (immunosuppressed) Latent infection diagnosed with PPD Treat latent disease with INH Treat active disease with multidrug regimen
81
Sarcoidosis •
Granulomatous disease
•
Immune-mediated
•
•
•
Granulomas form many places in the body
Immune cells play major role
Unknown cause
Sarcoidosis Jason Ryan, MD, MPH
Sarcoidosis •
•
•
Pathology
Hallmark is widespread non-caseating granulomas Tightly packed central area of macrophages, epithelioid cells, multinucleated giant cells Surrounded by lymphocytes, monocytes, mast cells, fibroblasts
•
Cell mediated immune process
•
Accumulation of TH1 CD4+ helper T cells •
•
•
•
•
•
Organ Involvement •
Lungs (most common) Skin
•
Eye
•
•
Conduction disease (heart block)
•
Cardiomyopathy
•
Many other systems rarely involved
•
Any system can be involved
•
Renal: Renal failure
•
CNS: Neurosarcoid, Bells Palsy, Motor loss
IFN-γ activates macrophages Ultimately leads to granuloma formation Key players: CD4 T cells, IL-2, IFN-γ
Lung Involvement •
Classic finding is hilar lymphadenopathy Classic symptom is cough, dyspnea
•
Can cause infiltrates
•
•
Heart •
High CD4:CD8 ratio
Secrete IL-2 and interferon-γ IL-2 stimulates TH1 proliferation
82
Can cause pulmonary fibrosis
Skin Involvement •
Many lesions possible •
•
Eye Involvement: Uveitis •
Plaques, maculopapules, subcutaneous nodules
Classic lesion is erythema nodosum •
Inflammation of fat cells under skin
•
Tender red nodules
•
Usually on both shins
Can involve many parts of eye
•
Classic is uveitis Uvea:
•
UveitisTypes
•
Often mild symptoms
•
Often detected on routine exam
•
•
•
Anterior (iris, ciliary)
•
Posterior (choroid)
•
Other Sarcoidosis Features •
•
•
hydroxylase activity in alveolarmacrophages
Elevated 1-
•
Increased vitamin D levels (calcitriol)
•
Non-specific finding Elevated in many lung diseases
25-OH Vitamin D
1α - hydroxylase 1,25-OH Vitamin D 2
Treatment •
•
Steroids Other immunosuppressants •
Methotrexate
•
Azathioprine
•
Mycophenolate
83
African American female
•
Hilar lymphadenopathy Cough, dyspnea
•
Often asymptomatic, detected on routine chest x-ray
•
High ACE levels •
Dry eye, blurry vision
Classic Presentation
Hypercalcemia •
Iris, ciliary body, choroid
Pulmonary Embolism •
Pulmonary Embolism
Thrombus in pulmonary artery
•
Rarely formed in heart or pulmonary vasculature Majority come fromfemoral vein or deep leg veins
•
Travels to lung via IVC RA RV
•
Jason Ryan, MD, MPH
Pulmonary Embolism •
Can be “unprovoked”
•
Often secondary to ahypercoagulable state •
Secondary: Malignancy, surgery, etc.
•
Primary: Protein C/S deficiency, ATIII deficiency, etc.
Pulmonary Embolism •
Chest pain
•
Respiratory distress
•
•
Dyspnea
•
Hypoxemia
•
•
Pulmonary Embolism
•
Dead space •
Ventilation without perfusion
•
V/Q = ∞
V/Q mismatch
•
Shunting
•
Hyperventilation Blood gas findings variable
•
Classic findings:low PaO2 and low PCO2
•
•
Thrombus within a deep vein Usually occurs in calf or thigh
•
Commonly femoral/popliteal veins
•
Many other V-Q disturbances •
Obstruction to flow through pulmonary arteries
Small, chronic emboli:p ulmonary hypertension
Deep Vein Thrombosis
Ventilation-Perfusion •
Tachypnea
Massive PE can causesudden death •
•
Classic presentation is pleuritic
•
•
•
84
Can extend or“grow” Precedes pulmonary embolism Often 2° hypercoagulable state
Deep Vein Thrombosis • • • • • •
Deep Vein Thrombosis
Often asymptomatic until PE
•
Calf pain Palpable cord (thrombosed vein)
•
•
Unilateral edema
•
Warmth, tenderness, erythema Homan’s sign: calf pain with dorsiflexion of foot
• Diagnosis: Lower extremity ultrasound
•
Used in high-risk DVT patients
•
Placed to prevent pulmonary embolism
“Venous thromboembolism” (VTE)
Prevention important in hospitalized patients •
Hypercoagulable
•
Immobility, stasis of blood, inflammation
Prophylaxis: SQ heparin, LMWH
S1Q3T3
IVC Filter •
Similar treatment to PE “DVT/PE”
S1Q3T3
Wells Score Active cancer
1
Immobilization of the lower extremities Recently bedridden
1
Localized tenderness
1
Leg swelling One leg swollen > other Pitting edema Superficial veins visible
1 1
Alternative diagnosis likely
-2
Score >=3 High Probability 1-2 Mod Probability 0 Low Probability
85
1
1 1
Pulmonary Embolism
D-dimer
Diagnosis
•
Degradation product of fibrin
•
CT angiogram
•
Sensitive but not specific (unidirectional)
•
VQ Scan
•
•
Levels elevated in DVT/PE
•
Levels also elevated in many, many other conditions
Useful when normal in setting of low-mod Wells score
Treatment DVT/PE
Patent Foramen Ovale
•
Initial treatment with heparin or LMWH
•
•
Transition to warfarin (oral)
•
•
Massive PE: thrombolysis (tPA)
•
Failure of foramen ovale to close after birth Can allow venous clot to reach arterial system (brain)
•
Rarely causesstrokein patients with DVT/PE
Fat Embolism •
•
•
Found in ~25% adults
Fat Embolism
Often occurs after a long bone facture
•
Fat may cross lungs small artery infarctions Fat embolism syndrome: pulmonary, neuro, skin •
•
86
Lung •
Dyspnea, hypoxemia
•
Diffuse capillary leak (ARDS)
•
Often requires mechanical ventilation
Neurological •
Usually confusion
•
May develop focal deficits
Petechiae
Amniotic Fluid Embolism •
•
•
•
Amniotic Fluid Embolism
During labor or shortly after
•
Amniotic fluid, fetal cells, fetal debris enter maternal circulation Inflammatory reaction Often fatal
•
Amniotic Fluid Embolism •
•
•
Phase II (hemorrhagic phase) •
Massive hemorrhage
•
DIC
Key feature:bleeding Seizuresalso often occur
87
Phase I •
Pulmonary artery vasospasm pulmonary hypertension
•
Right heart failure
•
Hypoxia
•
Myocardial capillary damage left heart failure
•
Pulmonary capillary damage ARDS
•
Acute respiratory distress syndrome
Key features:respiratory distress, ↓O2, hypotension
Chest X-ray •
Chest X-rays
Difficult to see different structures
•
Many, many normal variants Many,many pathologic findings
•
Reasonable goals:
•
•
Basic chest anatomy
•
Classic examples of pathology
Jason Ryan, MD, MPH
Chest Anatomy
Pulmonary Edema
Aortic Knob Pulmonary Artery SVC Left Atrium
Right Atrium
Left Ventricle IVC
Right Ventricle
88