Lectures 1-2/7-8 - Pulmonary Pathophysiology I-IV Flashcards
1
Q
2 types of airways? List parts for each.
A
- Upper: nose, pharynx, larynx
2. Lower: trachea, bronchi, lungs
2
Q
2 primary functions of the respiratory system? Describe each.
A
- Ventilation: air movement
2. Respiratory: gas exchange
3
Q
What is the respiratory membrane made of?
A
- Alveolar wall
- Capillary wall
- Basement membrane
4
Q
2 types of functional airways? Describe each.
A
- Conducting airways: nose to terminal bronchioles (0-16th branching) - no gas exchange
- Respiratory airways: respiratory bronchioles to alveolar sacs (17-23rd branching) - gas exchange
5
Q
Other name for conducting airways?
A
Anatomical dead space
6
Q
Which airway type is involved in obstructive airway disease?
A
Small conducting airways
7
Q
Which airway type has a larger proportion of smooth muscle than the other?
A
Small conducting airways
8
Q
What fraction of TV sits in the anatomical dead space under normal conditions?
A
1/3rd
9
Q
Which airways are considered small?
A
Those with a luminal diameter <2mm => 4-14th branching
10
Q
What is necessary for air to get into the lungs during inspiration?
A
Chest volume increases and pressure inside the lungs must be lower than atmospheric pressure
11
Q
Primary muscles of inspiration?
A
- Diaphragm
2. Intercostal muscles
12
Q
Primary muscles of expiration?
A
None
13
Q
What happens during expiration?
A
Diaphragm relaxes and lung elastic recoil decreases volume and increases intrathoracic pressure to push air out
14
Q
What is an important factor in removing air from the lungs?
A
Lung elasticity and recoil, which is dependent on elastic elements in lungs and surface tension
15
Q
What are the 6 factors controlling ventilation?
A
- Voluntary: phrenic nerve (somatic)
- CO2
- O2
- pH
- Lung stretch
- Pain
16
Q
What are the accessory muscles of respiration?
A
- Intercostal muscles
- Chest wall muscles
- Abdominal muscles
- Neck muscles
17
Q
How can one identify respiratory distress by simply observing the patient?
A
Look at accessory muscles of respiration and see if they are being recruited
18
Q
Which nerves carry sensory information from peripheral chemoreceptors to the brain to control respiration?
A
Cranial nerves 9 and 10:
- Vagus nerve
- Glossopharyngeal nerve
19
Q
What are the alveolar sacs lined with? Why is this important?
A
Small layer of water => creates surface tension, which is reduced by surfactant
20
Q
4 ways of examining the respiratory system? Describe each.
A
- Inspection: respiratory rate, respiratory distress (can the person talk normally?), even chest inflation, use of accessory muscles, cough, respiratory sounds, deformities of the chest wall, tracheal deviation
- Palpation: equal respiratory expansion, tactile fremitus
- Percussion: dull sounds vs. hyper-resonance
- Auscultation: pathological sounds (wheezes, crackles, ronchi etc), egophony
21
Q
Normal RR?
A
12-20
22
Q
What is tactile fremitus?
A
Tremulous vibration of the chest wall during speaking that is palpable on physical examination and indicates increased lung consolidation
23
Q
What is pulmonary consolidation?
A
Region of (normally compressible) lung tissue that has filled with liquid
24
Q
Anterior and posterior surface projections of right superior lobe?
A
Anterior = root of neck to above rib 4
Posterior = root of neck to above rib 6
25
Anterior and posterior surface projections of right inferior lobe?
Anterior = top of 4th rib to medial 6th rib
Posterior = top of rib 6 to top of rib 10 medially
26
Anterior and posterior surface projections of right middle lobe?
Anterior = laterally over rib 6 and 5th and 6th intercostal spaces
Posterior = none
27
Anterior and posterior surface projections of left superior lobe?
Anterior = root of neck to above 4th rib and then inverse C-shape to above rib 6
Posterior = root of neck to above rib 6
28
Anterior and posterior surface projections of left inferior lobe?
Anterior = over lateral 6th rib and 5th and 6th intercostal spaces above and below
Posterior = top of rib 6 to top of rib 10 medially
29
What is the forced expiratory volume? Notation? What kind of measure is this?
Volume of air exhaled in the first second of maximal expiration maneuver = FEV1
Measure of flow
30
What is the forced vital capacity? Notation?
Total volume of air exhaled during a forced expiration = FVC
31
What % of the FVC does the FEV1 comprise in a normal healthy individual? What will affect this normal number in healthy individuals?
FEV1/FVC = 75-80% (or within 10% of the normal expected number)
Factors affecting this number: age, height, race, and gender
32
What is the DLCO?
Diffusion capacity of the lungs for CO
33
How many lung volumes are there? Describe each. WHICH ONES ARE DIRECTLY MEASURED via spirometry?
1. ***Tidal volume (TV) = amount of air breathed out/in under normal conditions
2. ***Inspiratory reserve volume (IRV) = max amount inspired above the tidal volume
3. ***Expiratory reserve volume (ERV) = max amount expired below the tidal volume
4. Residual volume (RV) = remaining amount of air left after max expiration
34
How many lung capacities are there? Describe each. WHICH ONES ARE DIRECTLY MEASURED via spirometry?
1. Total lung capacity (TLC) = sum of all lung volumes = TV + IRV + ERV + RV
2. ***Vital capacity (VC) = largest breath you can take = TV + IRV + ERV
3. ***Inspiratory capacity (IC) = maximal inspiratory volume = IRV + TV
4. Functional residual capacity (FRC) = amount of air left after residual expiration = ERV + RV
35
What 4 arterial blood gas values measure functioning of the respiratory system? What are normal values for each?
1. pH (normal = 7.35 – 7.45)
2. PaO2 (normal = 75-100 mmHg)
3. PaCO2 (normal = 35-45 mmHg)
4. HCO3- (normal = 22-26 mEq/L)
36
What % of atmospheric air is O2? Notation? Does this vary with altitude?
Fraction of Inspired Oxygen = FiO2 = 21%
NOPE
37
2 types of lung diseases?
1. Restrictive
| 2. Obstructive
38
Describe restrictive lung disease.
Decreased compliance of lung tissue leading to difficulty in lung expansion
39
What is lung compliance?
Amount of pressure required to bring a certain volume change = ΔV/ΔP
40
How are PFT/arterial blood gas values affected by restrictive lung disease?
1. Decreased TLC
2. Decreased FVC
3. Normal FEV1/FVC ratio
4. Possible decreased DLCO
5. V/Q mismatch
6. Hypoxemia
41
Difference between hypoxia and hypoxemia?
Hypoxia = low CaO2
Hypoxemia = low PaO2
42
2 types of restrictive lung diseases? Describe each.
1. Extrinsic: chest wall restriction
| 2. Intrinsic: lung tissue damage
43
2 types of causes for extrinsic restrictive lung disease? Provide examples for each.
1. Neuromuscular: Guillain-Barre, myasthenia gravis, polio, muscular dystrophy
2. Non-muscular: chest wall deformity, obesity, pain
44
3 causes for intrinsic restrictive lung disease?
1. Toxin exposure: airway irritants, drugs, radiation
2. Systemic disease
3. Unknown
45
What is intrinsic restrictive lung disease often accompanied by?
Decreased diffusion capacity
46
Describe the pathophysiology of intrinsic restrictive lung disease.
Chronic inflammation => excessive fibrous connective tissue (aka scarring) in the lungs => stiffening of lung and decreased compliance = pulmonary fibrosis
47
What is pectus excavatum? What is it an example of?
Congenital chest wall deformity in which several ribs and the sternum grow abnormally, producing a concave, or caved-in, appearance in the anterior chest wall
Example of non-muscular extrinsic restrictive lung disease
48
What is idiopathic pulmonary fibrosis? How common is it? Who is affected by it?
Progressive and chronic inflammation of lung tissue with unknown cause in which inflammation precedes fibrosis with over activation of immune cells in the lungs
Affects adults over 40 with median survival of 2-4 years (progresses fast), rare
49
What is idiopathic pulmonary fibrosis histologically linked to?
1. Overproduction and disorganization of collagen and ECM = fibrosis
2. Destruction of pulmonary structure
50
Clinical presentation of idiopathic pulmonary fibrosis?
1. Symptoms of worsening dyspnea
2. Restrictive pattern on PFTs
3. Characteristic findings on imaging: honeycomb lung and reduced lung volume
4. Characteristic findings on lung biopsy
51
Treatments for idiopathic pulmonary fibrosis?
1. Supportive care: vaccination, oxygen, pulmonary rehab
2. Inclusion in clinical trials, steroids and other immunosuppressive therapy may slow progression
3. Lung transplant
52
What is pneumoconiosis?
Inhalation of inorganic dust causing intrinsic restrictive lung disease
1. Coal => black lung
2. Silica (ore processing) => silicosis
3. Asbestos (farm workers, households) => asbestosis
53
What toxin exposure is also linked to lung cancer?
Asbestos
54
Is pulmonary fibrosis reversible?
NOPE
55
What is hypersensitivity pneumonitis?
Allergic alveolitis (inflammatory response) to a number of organic agents including dusts, grains, animal feces, molds, avian antigen causing intrinsic restrictive lung disease
56
3 examples of hypersensitivity pneumonitis?
1. Molds/dust from coffee beans, tea plants, grapes, cheese, potatoes => farmer's lung
2. Pigeon breeders
3. Air ventilation and water-contaminants
57
How to diagnose intrinsic restrictive lung disease due to exposure?
1. History of exposure to substance (> 10 yrs) - occupational history is important
2. Keep in mind patients may be asymptomatic despite findings on exam/imaging/PFTs
58
4 symptoms of intrinsic restrictive lung disease due to exposure?
1. Dyspnea
2. Cough
3. Fatigue
4. Weight loss
59
How to treat intrinsic restrictive lung disease due to exposure?
1. Avoid exposure to stop progression
| 2. Supportive care, corticosteroids to inhibit the immune system
60
How to diagnose intrinsic restrictive lung disease due to systemic disorders?
1. Involvement of other organs
2. Antibody titers
3. Other disease specific features
61
How to treat intrinsic restrictive lung disease due to systemic disorders?
1. Specific disease treatment
| 2. Steroids
62
Example of a systemic disease that causes intrinsic restrictive lung disease?
Sarcoidosis
63
What is sarcoidosis? What is it caused by? What patients get it?
Systemic disease with unknown cause characterized by noncaseating granuloma (immune cell collection) formation, with the healing of granulomatous tissue leading to fibrotic changes
Onset < 40 yo, more common in women, AA race
64
Where is sarcoidosis found in the body?
Can be found in all tissue but very common in lungs and lymph nodes (90%)
65
X-ray presentation of sarcoidosis?
Bilateral hilar adenopathy
66
Describe the progression of sarcoidosis.
Unpredictable course:
1. Can regress on its own
2. Some require therapy including immunosuppressive agents (~ 70%) but fully recover
3. Can become chronic and lead to pulmonary fibrosis and death (~10-15%)
67
Who gets sarcoidosis?
Black women before 40 yo is most common
68
What causes granulomas to form?
Antigen that the body cannot break down
69
Other than in sarcoidosis, in what other disease are granulomas seen?
Tuberculosis
70
What is the antigen that the body is attacking in sarcoidosis?
Unknown
71
Describe obstructive lung disease.
Airway obstruction
72
How are PFT/arterial blood gas values affected by obstructive lung disease?
1. Decreased FEV1
2. Decreased FEV1/FVC ratio
3. Possible elevated RV and TLC due to gas trapping
73
2 types of obstructive lung diseases?
1. Asthma
| 2. COPD: chronic bronchitis + emphysema
74
Describe asthma.
Reversible airway obstruction (usually expiratory), inflammation and hyper-responsiveness to allergens due to a complex, abnormal, and exaggerated inflammatory response with many immune cells and mediators involved
Inflammation leads to smooth muscle constriction, increased airway edema, and thickened mucus
75
Which airways are preferentially affected in asthma?
Small airways
76
What are some triggers for asthma attacks?
1. Viral respiratory infections: RSV, rhinovirus
2. Allergens: dust, pets, cockroaches, molds, occupational etc.
3. Others: cold air, exercise, irritant exposure (e.g. smoking)
77
What is the pathogenesis of asthma? What to note?
1. Immediate phase reaction: over activation of TH2 => IgE production by plasma cells to specific allergens => degranulation of mast cells which release histamine, prostaglandins, and leukotrienes => bronchoconstriction and mucus production/inflammation
2. Late phase reaction: recruitment of other immune cells (especially eosinophils) => vasoconstriction and epithelial damage
Note: other triggers can cause airway inflammation through non-IgE mechanisms
78
Effect of leukotrienes on the lungs?
Bronchoconstriction
79
Clinical presentation of asthma?
1. History: episodes of dyspnea, chest tightness, coughing, increased respiration rate (tachypnea), wheezing
2. Exam: wheezing and poor-air movement on auscultation, accessory muscle use, tachypnea
3. Blood gas: hypoxemia and respiratory alkalosis due to hyperventilation, can progress to acidosis as obstruction worsens
4. PFTs: obstruction may not be seen between episodes
80
What is cough variant asthma?
Presents as cough only
81
What is exercise variant asthma?
Induced only with exercise
82
What is status asthmaticus?
Prolonged asthma exacerbation unresponsive to therapy
83
Asthma risk factors?
1. Genetic
2. Concurrent atopy, food allergies => predilection to develop IgE response to allergens
3. Prematurity
4. Lack of exercise
5. Exposure: early exposure to allergens, pollution, smoking, viral infection
6. “Hygiene hypothesis”: early exposure to antibiotics, “cleaner” households, C-section delivery, declined infection exposure (especially parasites), declined outdoor play time
84
What is atopy?
1. Asthma
2. Allergic rhinitis
3. Eczema
85
What 7 factors are used to grade asthma severity?
1. Symptoms
2. Nightime awakenings
3. Short-term acting beta-agonist use for symptom control
4. Interference with normal activity
5. Lung function
6. Need for corticosteroids
7. History of intubation, hospitalization
86
5 asthma therapies?
1. Avoidance of triggers
2. Short and long acting beta-agonist (to activate sympathetic NS response): dilation of smooth muscle in the bronchi
3. Inhaled and oral corticosteroids: reduce bronchial inflammation
4. Leukotriene antagonists: inhibit steps in inflammatory pathway
5. Immune modulating antibodies block IgE
87
2 types of asthma therapies?
1. Acute therapy
| 2. Maintenance therapy
88
What is aspirin sensitive asthma?
Some patients' asthma will be triggered by aspirin, because it inhibits the synthesis of thromboxanes/prostaglandins from arachidonic acid leading to the increased synthesis of leukotrienes causing bronchoconstriction
89
How to determine what asthma treatment is appropriate?
Step-wise approach
90
Why are long-acting beta agonists never used alone to treat asthma?
Because they increase the risk of death from asthma, maybe because they desensitize airways to beta-agonists so they are given with inhaled corticosteroids, which decreases the risk
91
Describe the 5 steps of managing an acute asthma exacerbation.
1. Short-acting beta agonists (SABA) (inhaled or nebulizer) and Ipratropium (anti cholinergic)
2. Supplemental oxygen
3. Systemic steroids (glucocorticoids)
4. Systemic beta agonist (epinephrine)
5. Intubation and mechanical ventilation
92
When an asthma patient stops wheezing, does it mean he is getting better?
Not necessarily because it could mean the airflow is so low you can no longer hear wheezing
93
Do most COPD patients have both emphysema and chronic bronchitis?
Most patients have some element of both (with one predominating)
94
Risk factors for COPD?
1. Smoking (80% of COPD patients)
| 2. Lung irritant exposure
95
4 symptoms of COPD?
1. Progressive dyspnea
2. Cough
3. Wheezing
4. Weight loss
96
How to diagnose COPD?
1. PFT (reduced DLCO in emphysema) - helpful to stage the disease
2. Hyperinflation on imaging (due to expiratory obstruction causing gas trapping)
3. History when other causes ruled out
97
Describe chronic bronchitis?
Airway obstruction with:
1. Chronic cough
2. Bronchial inflammation
3. Production of thick mucus
98
Pathophysiology of chronic bronchitis?
Chronic exposure to irritants leads to mucus hypersecretion and increase in mucus producing cells over time =>
1. Persistent inflammation increases bronchospasm response
2. Excess mucus impedes ciliary function and increases infection risk, triggering episodic exacerbations
99
Smoking DIRECT effect on the lungs?
Directly inhibits ciliary function and mucus clearance
100
Clinical presentation of chronic bronchitis?
1. Chronic, productive cough and later dyspnea
2. Increased respiratory infections
3. Obstruction on PFTs with gas trapping as disease progresses
4. Hypoxemia leading to digital clubbing, cyanosis, and cardiac manifestations
5. Decreased respiratory drive leads to hypoventilation and increase CO2 retention => chronic hypercapnia => reset of respiratory centers => ventilation more sensitive to O2 status
101
Which disease has more gas trapping: chronic bronchitis or emphysema?
Emphysema
102
Why do we call chronic bronchitis patients "blue bloaters"?
1. Cyanotic due to hypoxemia
2. Fluid retention due to alveolar hypoxia => pulmonary vasoconstriction => pulmonary HT => low CO => decreased circulating BV => RAAS activation
103
Are emphysema patients blue bloaters like chronic bronchitis patients? Explain.
NOPE, because they can compensate for the hypoxemia
104
What is digital clubbing?
Angled finger beds
105
Why do chronic bronchitis patients have cardiac manifestations?
Because their hypoxia can cause pulmonary HT
106
What is emphysema?
Enlargement and destruction of alveolar units in lung without major fibrosis with loss of elastic tissue in lungs => dysfunctional recoil + ineffective expiration:
- Destruction of capillary-alveoli interface leads to diffusion abnormalities (decreased DLCO)
- Alveoli hyperinflation leads to air spaces in the pleura and lungs
- Increase in lung compliance => increased work of breathing => dyspnea, cachexia, pursed-lip breathing and accessory muscle use
107
2 types of emphysema? Describe each. What do they have in common?
1. Primary: genetic alpha I anti-trypsin deficiency
2. Secondary: exposure to smoking, pollutants
Similar disease progression
108
Why is emphysema an obstructive lung disease?
Because the loss of recoil causes a functional obstruction for air to be expired
109
What is the role of alpha I anti-trypsin protein?
Responsible for inhibiting specific protein breakdown (elastin)
110
Why does an alpha I anti-trypsin deficiency lead to emphysema?
Increased elastase activity => tissue architecture disruption + liver damage/renal/GI disease
111
How does smoking affect emphysema type 1 patients?
increases risk and severity
112
Profile of patients with emphysema type 1? What to note?
Patients with emphysema under 45 yo, non-smokers and with a family history
Note: very rare
113
How does smoking cause emphysema?
1. Smoking increases neutrophils in lungs and stimulate release of elastase granules
2. Free radicals both in neutrophils and smoking contaminants inhibit alpha-1 anti trypsin
114
Clinical presentation of severe air-trapping in emphysema patients?
Barrel chest = increased AP diameter + hyper-resonant sounds
115
Main difference between chronic bronchitis and emphysema?
Emphysema comes with diffusion capacity decrease
116
2 histological classes of emphysema? Describe each. Which is most common?
1. Panacinar emphysema:
- Entire acinar unit involved
- Lower lung lobes
- Alpha 1 antitrypsin deficiency, older smokers
2. ***Centriacinar emphysema:
- Respiratory bronchioles and alveolar ducts
- Upper lung lobes
- Smokers
117
Why do we call emphysema patients "pink puffers"?
1. Pink: relatively well oxygenated blood until late stage because they have a matched V:Q defect (decreased ventilation due to increase in lung compliance and decreased perfusion due to destruction of capillary beds)
2. Puffer: air-trapping and hyperventilation to compensate for V:Q defect
118
PFT values for emphysema?
1. Decreased DLCO
2. Increased RV
3. Increased TLC
4. Decreased VC
119
What does cachexia mean?
Severe weight loss
120
Are blood gases normal or abnormal in emphysema patients?
Normal at rest because of compensatory hyperventilation
121
What are bullae?
Empty spaces filled with air in the lungs in emphysema patients
122
Effect of emphysema on diaphragm?
Flattened diaphragmatic borders due to hyperinflation
123
How to clinically manage COPD? 10 interventions.
1. Avoidance of pollutant exposure (stop smoking)
2. Vaccination to prevent infections
3. Pulmonary rehabilitation: helps patients use their lungs efficiently
4. Bronchodilators
5. Anticholinergics
6. Inhaled and oral steroids
7. Expectorants: help clear mucus from airways (make cough more “productive”)
8. Antibiotics
9. Supplemental oxygen to avoid pulmonary HT and cardiac manifestations BUT be careful with respiratory drive and smokers!
10. Lung volume reduction surgery
124
When an emphysema patient stops smoking, will function be re-gained?
NOPE - it'll just stop disease progression
125
3 pulmonary vascular diseases?
1. Pulmonary embolism and infarction
2. Pulmonary HT
3. Pulmonary edema
126
What does pulmonary HT lead to in the final stages?
Cor pulmonale = RIGHT ventricular heart dysfunction (dilation, hypertrophy) due to the back up of fluid/pressure into the right side of the heart causing increased work
127
What is pulmonary edema?
Fluid in alveoli
128
2 types of pulmonary edemas? Describe each. How to tell difference between the 2?
1. Cardiogenic: caused by elevation of capillary hydrostatic pressure from left heart dysfunction
2. Non-cardiogenic: normal cardiac function, usually from lung injury and increased capillary permeability (e.g. ARDS, high altitude, neurogenic, narcotics, PE)
To tell the difference: right-heart catheterization to measure pulmonary artery wedge pressure to see if the LAP is elevated => if it is: cardiogenic
OR BNP, ECG, X-ray (enlarged cardiac size, septal lines, edema distribution), echo (valvular function and size of cardiac chambers)
129
What is the difference between pulmonary edema and pleural effusion?
Pulmonary edema: fluid in alveoli
Pleural effusion: fluid in pleural space
130
What causes ARDS most commonly?
Sepsis = systemic inflammatory response in the presence of a known or suspected infectious agent
131
What are 3 causes of left heart dysfunction?
1. Valvular dysfunction
2. Reduction in left ventricular contractility
3. Dilated cardiomyopathy
132
Equation to measure net movement of fluids across the alveolar-capillary interface?
Jv = Kf . [Pc-Pi - σ.(πc-πi)]
Pc is the capillary hydrostatic pressure
Pi is the interstitial hydrostatic pressure
πc is the capillary oncotic pressure
πi is the interstitial oncotic pressure
Kf is the filtration coefficient – a proportionality constant
σ is the reflection coefficient
133
Describe the pathophysiology of cardiogenic pulmonary edema?
Increase in capillary hydrostatic pressure => increase in fluid movement from capillary to alveoli
134
Describe the pathophysiology of non-cardiogenic pulmonary edema?
Damage to interface between capillary and alveoli => wider gaps => increase in Kf => allows fluid and proteins to enter the alveoli
135
How is pulmonary capillary hydrostatic pressure affected in non-cardiogenic pulmonary edema?
It is not affected
136
Clinical presentation of pulmonary edema? Is it the same for both types? Implication?
1. Dyspnea
2. Tachypnea
3. Hypoxemia
4. Cough (with fluid)
5. Crackles and other abnormal sounds
6. JVD: jugular venous distention
Similar presentation between different ideologies, history should focus on primary insult
137
Can patients have both types of pulmonary edema?
In some complicated situations, YUP
138
What is a BNP test?
Chemical released by heart during heart failure (ANP) so would be elevated in cardiogenic pulmonary edema
139
What is the most common cause of non-cardiogenic pulmonary edema?
ARDS = acute respiratory distress syndrome
140
What is ARDS?
Acute respiratory failure from acute lung injury and inflammation causing diffuse alveolar damage (injury of alveolar capillary membrane) =>
1. Increased alveolar capillary permeability => non-cardiogenic edema
2. Prevents normal gas exchange => hypoxemia
3. Fluid increases surface tension => increase in alveolar collapse => decreases compliance
4. Hypoxic vasoconstriction, lung element destruction => increases pulmonary artery pressure
141
Why is ARDS called an acute restrictive lung disease?
Because of the decreased compliance caused by the alveolar-capillary membrane damage leading to fluid and increased surface tension
142
What group of diseases is ARDS the most severe of?
Most severe spectrum of ALI = acute lung injury
143
What is the role of the immune system in ARDS?
Lung injury => activation of inflammatory pathways => neutrophil recruitment + release of chemicals => further promote lung inflammation and damage
144
What are the 4 stages of ARDS? Describe each.
1. Exudative: diffuse alveolar damage (DAD), edema, hyaline membrane (necrotic cell debris, fibrin)
2. Proliferative: edema resolves, cellular proliferation and collagen deposition
3. Fibrotic: fibrotic changes and loss of lung architecture
4. Resolution: surviving patients regain lung function, weeks to months with possible lung impairment
145
How acute is ARDS?
Literally happens in one day
146
Mortality rate for ARDS? What does it depend on? What to note?
Very high because systemic insult: 40% even with treatment
Depends on cause, severity and co-morbidities
Note: many patients die from primary illness, multi-organ failure, shock etc. rather than respiratory failure
147
What are the criteria to diagnose SIRS? What does it stand for?
SIRS: systemic inflammatory response syndrome (in response to sepsis)
2 or more of the following:
1. Body temp deregulation
2. High HR
3. High RR
4. WBC count
148
11 possible causes of ARDS? Most common?
1. Aspiration pneumonia: aspiration of gastric content into lungs
2. Pneumonia
3. Multi-organ trauma (lung contusion)
4. Burns
5. Near drowning
6. Inhalation of toxic irritants, smoke
7. Drugs/alcohol overdose
8. Pancreatitis
9. Multiple blood transfusion, transfusion-related acute lung injury
10. Emboli
11. Sepsis***
149
Why is it hard to treat ARDS patients?
Causative processes may be simultaneously causing systemic vasodilation (shock) and multi-organ dysfunction (MODS)/failure
150
What does MODS stand for?
Multi-organ dysfunction syndrome
151
Clinical presentation of ARDS?
1. Acute onset dyspnea and hypoxia 24-48 hours after injury or infection => shortness of breath, hypoxemia, tachycardia, tachypnea, accessory muscle use etc.
2. Bilateral infiltrates
3. PaO2/FiO2 ratio decreased indicating poor transfer of oxygen to blood and refractory to oxygen supplementation
152
3 criteria to diagnose ARDS?
1. Timing: within 1 week of a known clinical insult or new or worsening respiratory symptoms
2. Chest imaging: bilateral opacities that are not fully explained by effusions, lung collapse, or nodules
3. Origin of edema: respiratory failure not fully explained by cardiac failure or fluid overload
153
How is ARDS graded?
By oxygenation measure (PaO2/FiO2)
154
ARDS treatment?
1. Identification and treatment of underlying cause
2. Supportive care: sedation, fluid monitoring, prevention of DVT and GI bleed, treatment of nosocomial infections etc.
3. Mechanical ventilation with high FIO2
155
How to improve ARDS outcomes? 2 interventions
1. Protective ventilation
| 2. Fluid management
156
What are some common complications of mechanical ventilation of ARDS patients?
1. VALI = ventilator-associated lung injury
2. Nosocomial infection
3. DVT
4. Stress GI ulceration
157
What are the 5 mechanisms of VALI?
1. Barotrauma = increased positive pressure
2. Volutrauma = over-distention of alveoli by high TV
3. Mechanical shear stress = cyclic closing and reopening of alveoli
4. Biotrauma = inflammatory mediators released by shear stress
5. O2-toxicity = due to toxic oxygen radicals
158
What are the concepts of protective ventilation?
1. Avoid VALI mechanisms
2. Plateau pressures <=30 cm H2O
3. TV of 6 mL/kg predicted body weight
4. Keep alveoli open by PEEP
5. Try spontaneous breathing early
159
Normal PEEP?
0 cm H2O
160
Definition of pulmonary HT?
Pulmonary artery mean pressure above 25 mmHg (normal 8-20 mm Hg)
161
3 pathophysiologies/causes of pulmonary HT? Which 2 are reversible?
1. ***Imbalance between vasodilation and vasoconstriction
2. ***Hypertrophy of smooth muscle in pulmonary arteries => luminal narrowing and increased pressure
3. Arterial atherosclerosis: remodeling of arteries with fibrotic tissue
162
5 groups of causes for pulmonary HT?
1. PAH
2. Left heart dysfunction
3. Lung disease/chronic hypoxemia
4. Pulmonary vasculature occluded by clots
5. Multifactorial
163
Secondary effect of pulmonary HT?
Right heart hypertrophy
164
Describe PAH causing pulmonary HT. What does it stand for?
Pulmonary Arterial HT
Disease localized to the pulmonary arterioles due to:
1. Idiopathic (rare)
2. Familial
3. Persistent pulmonary HT of the newborn
165
What is PAH associated with?
1. Collagen vascular disease
2. Congenital systemic to pulmonary shunts
3. Portal HT
4. HIV
5. Drugs/toxins
6. Significant venous or capillary involvement (e.g. pulmonary veno-occlusive disease, pulmonary capillary haemangiomatosis)
166
Describe left heart dysfunction causing pulmonary HT. Diagnostic measure?
Increase in pressure in pulmonary vasculature needed to maintain forward driving force against dysfunctional left heart:
- Left atrial or ventricular heart disease
- Left sided valvular heart disease
Diagnostic measure = elevated pulmonary capillary wedge pressure
167
Describe lung disease/chronic hypoxemia causing pulmonary HT.
1. Chronic hypoxia => decreases endothelial nitric oxide synthase => less NO (vasodilator) => increase in arachadonic acid pathways and endothelin release => increases smooth muscle calcium concentration
2. Lung diseases: COPD and interstitial lung disease
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Why are COPD patients more likely to get pulmonary HT than emphysema patients? What to note?
Because COPD patients cannot compensate for hypoxemia, and emphysema patients can
Note: late emphysema can lead to pulmonary HT via alveolar/vascular bed destruction, hyperinflation and increased intra-alveolar pressure
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Effect of short-term hypoxia on the lungs?
Short term hypoxia => vasoconstriction to limit blood flow to poorly oxygenated lung
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What happens to the lungs after persistent pulmonary HT? What is this called?
Irreversible changes and replacement of blood vessel tissue with collagen = onion skinning in histology
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Clinical presentation of pulmonary HT? What to note?
1. Fatigue
2. Chest pain
3. Dyspnea
4. Tachypnea
5. Cough
6. Peripheral edema
7. Various heart murmurs
Note: may be masked by primary disease
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How to make a pulmonary HT diagnosis?
1. ECG indicates right ventricular hypertrophy
2. Enlarged right heart border and pulmonary vasculature on X-ray/echo
3. Definitive diagnosis by right heart catheterization and measurement of pulmonary artery pressure
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What is pulmonary HT treatment based on? Explain.
Treatment based on grouping classification:
1. Control of causative disorder (i.e. diuretics, anti-hypertensives for heart failure, anti-coagulants for chronic thrombi)
2. PH directed therapy: endothelin blockers, NO agonists, prostacyclin analogs
3. Lung transplantation for idiopathic PAH
4. COPD with PH: long term O2 therapy, but not all patients respond, especially if long term remodeling
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What is the most common cause of cor pulmonale?
COPD
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What % of COPD patients have cor pulmonale? In which patients is it more likely?
20-30%
More likely in patients with more severe airway obstruction and disease progression
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Core pulmonale treatment?
1. Treat the pulmonary HT
| 2. CV support
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Other name for cor pulmonale?
Pulmonary heart disease
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What is persistent pulmonary HT of the newborn (PPHN)? Why is it called that?
Called persistent because fetal circulation has NORMAL pulmonary HT due to elevated pulmonary vascular resistance (PVR) to keep blood out of the fetal lungs => fetal lungs have low oxygen tension, are fluid-filled, their balance of vasodilators/vasoconstrictors is in favor of vasoconstriction, and there are 2 bypass shunts (FO and DA)
In PPHN, there is a persistent elevated PVR causing a right to left shunt (either through FO or DA) and hypoxic respiratory failure
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What are the 2 vascular transitions at birth under normal conditions?
1. Rise is SVR due to the removal of the placental circulation (low resistance system) and sympathetic effects from the stress of birth
2. Decrease in PVR due to expansion and oxygenation of lung tissue, removal of fluid from fetal lungs, vasodilatory factors favored and remodeling of blood vessels to favor vasodilation, and bypass shunts close
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What are 6 potential causes of the elevated neonatal PVR in PPHN?
1. Vasoconstriction: imbalance of vasoactive substances causing constriction with normal lung architecture (acute problems) => asphyxia, pneumonia sepsis (due to Group B strep), meconium aspiration, respiratory distress syndrome
2. Remodeling of vasculature: smooth muscle proliferation, collagen deposition (chronic problems) => diaphragmatic hernia, chronic intrauterine hypoxia, antenatal ductal closure
3. Decreased lung size: decreased number of pulmonary vessels cannot accommodate right heart CO => diaphragmatic hernia, intrathoracic space occupying lesions, or chronic oligohydramnios due to renal dysfunction
4. Intravascular obstruction: hyperviscosity or polycythermia
5. Idiopathic
6. Maternal medication use: NSAIDs and SSRIs
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3 causes of hypoxic respiratory failure in PPHN?
1. Right to left shunt
2. High PVR so poor lung perfusion
3. Original cause of PPHN
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Why can meconium aspiration cause PPHN?
1. Promotes inflammation
2. Inhibits surfactant
=> vasoconstriction
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Why can NSAIDs cause PPHN?
Because they are COX inhibitors, which cause DA to close prematurely => increase blood flow to fetal lungs during development => shear stress => vasoconstriction
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Most common cause of PPHN?
Meconium aspiration
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Clinical presentation of PPHN?
1. Cyanosis
| 2. Fluctuating hypoxemia: frequent desaturation and large changes in PaO2
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In what infants do we see PPHN?
Term or post-term infants
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How to make a PPHN diagnosis? Which method is most significant? 3 methods.
1. ***Echo confirmation of R->L shunt
2. Need to confirm normal cardiac anatomy to exclude heart disease
3. Pulmonary artery pressure can be estimated - this alone is not a diagnosis!
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Treatmens for PPHN?
SUPPORTIVE CARE:
1. Oxygen: FIO2 100% to promote vasodilation of pulmonary vessels
2. Sedation to prevent agitation, which is associated with O2 drop
3. Ventilator support to remove CO2, as respiratory acidosis promotes vasoconstriction
5. Fluid and BP support, Hb optimization
INTERVENTIONS:
1. Surfactant
2. Inhaled NO and other vasodilators
3. ECMO: extracorporeal membrane oxygenation
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How to assess the need for ECMO?
Oxygenation index = Mean airway pressure in cm of water × FIO2 × 100/PaO2 [in mm Hg]
A high OI indicates need for ECMO
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What is ECMO?
Oxygenation and removal of CO2 wastes outside the body, for long-term use (days)
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Outcome of PPHN treatments?
High proportion of surviving infants have future disabilities (delay, motor etc)
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What is pulmonary embolism?
Occlusion of pulmonary vasculature by embolism from origin outside of lung
Can be blood (thrombus), fat, air, bone
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Most common cause of PE?
Thrombus from deep venous thrombosis (blood clot in the deep veins - DVT) of lower limbs
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2 types of PE?
1. Acutely occurring
| 2. Chronic (small PEs over time)
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Risk factors for DVTs? What is this called?
Virchow’s Triad:
1. Venous stasis: prolonged immobility
2. Hypercoagulation: cancer, pregnancy, estrogen contraceptives, congenital thrombophilia, systemic diseases (lupus, autoimmune), smoking
3. Vascular endothelial injury: surgery, IV line, medication
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Risk factors for PE?
Same ones as for DVTs = Virchow's Triad
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Describe the pathogenesis of PE.
1. V/Q mismatch due to increase in dead space => hypoxemia due to
- Impaired gas exchange
- Inflammatory response induced by the embolus that furthers vasoconstriction and diminishes surfactant secretion => atelectasis
2. Increased PVR causing:
- Reduced CO and hypotension
- Pulmonary HT
- Right heart dysfunction, especially with severe vascular obstruction
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Clinical presentation of PE? What to note?
1. Dyspnea (acute onset)
2. Pleuritic chest pain
3. Tachypnea
4. Tachycardia
5. Anxiety
6. Can present in shock or sudden death
7. Presence of symptomatic DVT (swollen, erythematous, tender calf) but not always identifiable
NOTE: may be asymptomatic
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How to make a PE diagnosis? Which method is most significant?
1. Chest x-ray (non-specific)
2. ECG
3. Elevated D-dimer: sign of clot degradation, only helpful if negative because many things can cause it to be elevated
4. ***CT-PA = pulmonary angiography or V/Q scan
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Treatment for PE?
1. Anti-coagulation therapy: acute and out-patient
2. Thrombolytic therapy for severe PE
3. Prevention of risk factors
4. IVC filter for embolism removal to prevent further clots
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What is a pulmonary angiography? What will it show if a patient has PE?
CT scan with contrast to visualize pulmonary arteries
PE would appear as saddle embolism if the clot is very large and blocks the pulmonary trunk
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What is a V/Q scan?
Uses radionucleotides:
1. Inhalation for V
2. IV injection for Q
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Risk of thrombolytic therapy?
Bleeding
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How does anti-coagulation therapy work?
Targets the blood coagulation cascade with specific drugs like warfarin, coumadin, or heparin to increase the INR to 2.5 seconds
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What is the INR?
International Normalized Ratio => measure of how long it takes the blood clotting cascade to be activated compared to normal: prothrombin time
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Length of anti-coagulation therapy?
3 months and then re-assess using D-dimer
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What is the pulmonary acinus?
All branches past the terminal bronchioles
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Why does hypoxia cause high RBC count?
Hypoxia signal on kidneys => signal to bone marrow to produce more RBCs to improve O2 delivery
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2 symptoms of right heart dysfunction?
1. Distended neck veins
| 2. Enlarged tender liver
210
2 symptoms of hypercapnia?
1. Somnolence
| 2. Personality changes
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How to tell if the DA is patent in PPHN?
Preductal vs postductal PaO2: if the difference is of >20 mmHg, or 10% saturation then it is patent:
- Measure PaO2 in right radial artery vs umbilical artery
- Measure O2 sat in right thumb vs toes
