Pulmonary Flashcards
1
Q
Why respiratory system - respiratory function
A
Gas transport for metabolism
2
Q
Why respiratory system - non respiratory function
A
Filtering and metabolism
3
Q
Stages of gas transport
A
Ventilation
Lung diffusion
Circulation
Tissue diffusion
Internal respiration
4
Q
Stages of gas transport - ventilation
A
Movement of bulk airflow from atmosphere into lungs and vice evrsa
5
Q
Stages of gas transport - lung diffusion
A
Gas exchange between respiratory zone and plasma/RBC across alveolar membrane
6
Q
Stages of gas transport - Circulation
A
Blood flow carries gas to and from tissues
7
Q
Stages of gas transport - tissue diffusion
A
Movement of oxygen from blood supply to tissue
CO2 from tissue to blood supply
8
Q
Stages of gas transport - Internal respiration
A
Cellular metabolism using O2 and producing CO2 –> generates energy
9
Q
Upper respiratory tract - function
A
Gas humidification, filtration, warming
Nasal passages
Air turbulence
10
Q
Conducting airways function
A
Gas distribution to respiratory zone
No diffusion of gas
11
Q
Airway patency based on structure: Trachea, bronchi, bronchioles
A
Trachea - cartialage arches (tracheal rings)
Bronchi - cartilage plates
Bronchioles - no cartilage, depend on lung recoil
12
Q
Airway clearance mechanisms
A
Bronchi - Cilia and bronchial glands clear contaminants
Distal conducting airways - cilia and goblet cells
Defensins - innate lung immunity
13
Q
Ventilatory pump contents
A
Rib cage and spine
Diaphragm
Intercostal muscles
Abdominal muscles
Accessory muscles
Visceral and parietal pleura and pleural fluid
14
Q
Ventilatory pump - rib cage and spine
A
Walls of pump
Increase volume of chest cage during inspiration
Posture
15
Q
Ventilatory pump - Diaphragm
A
Generates significant negative pressure for inspiration
16
Q
Ventilatory pump - Intercostal muscles
A
External intercostals - chest wall expansion
Internal intercostals - Exhalation
17
Q
Ventilatory pump - Abdominal muscles
A
Muscles of expiration
Utilized in lung disease or vigorous exercise
18
Q
Ventilatory pump - Accessory muscles
A
Used in lung disease or exercise
Tripod sitting - Lean forward on table/desk to stabalize shoulder girdle and neck/shoulder to act on chest wall
19
Q
Ventilatory pump - Parietal pleurae and pleural fluid
A
Visceral pleura - lies on lung, no pain fibers
Parietal pleura - covers inside of rib cage, pain fibers
Pleural space normally closed but can open/fluid filled in disease states
Pleural fluid acts as lubricant between two pleura
20
Q
Quiet breathing
A
Diaphragm contracts –> thorax volumed expands –> pleural space pressure decreases below atmospheric –> lungs expand and alveoli increase volume (negative pressure) –> air flows down airways into alveoli
Inspiratory muscles relax –> lung recoils –> alveoli decrease volume (pressure increases) –> air flows out of lung
21
Q
Exercise/lung disease breathing
A
Expiration may become active
Abdominal muscles and internal intercostals used –> further alveoli compression and expiration
22
Q
Repiratory zone: Contents and characteristics
A
Respiratory bronchioles, alveloar ducts, alveoli - gas exchange
Large surface area
Large volume of gas maintain diffusion pressure gradient
Very thin membrane
23
Q
Thin alveolar blood gas barrier contents
A
Respiratory epithelium
INterstitial space
Capillary endothelium
Plasma
Erythrocyte
24
Q
Gas diffusion and heart pumping
A
Oscillating nature of heart provides energy to gas in small airways and increases diffusion
25
Non respiratory function of lung - Maintenece and defense
Keeps itself clean via cleansing mechanisms and innate/adaptive immunity
Constant turnover and remodeling
Surfactant to maintain alveolar compliance
26
Non respiratory function of lung - filtering
Small capillaries can filter out physical material (clots, foreign bodies etc)
27
Non respiratory function of lungs - chemical processing
Hormone production: ACTH, prsotaglandings, vasoactive peptides, GF, serotonin
ACE
Arachiadonic acid release after pulomnary endothelium damage
28
Physiological dead space
Sum of:
Anatomic dead space (conducting airways)
Gas in NON PERFUSED alveoli (no gas exchange occurs)
29
Alveolar ventilation and PaCO2
Inversely proportional
Double alveolar ventilation = halved arterial CO2
Halved alveolar ventilation = double arterial CO2
30
Driving force of oxygen between alveoli and capillary
60mmHg towards capillary
31
Driving force of CO2 between alveoli and capillary
5mmHg towards alveoli
32
Perfusion limitation
Diffusion is controlled by perfusion
No blood flow = equilibration of gasses and no more diffusion
33
Conditions that cause O2 transfer to become diffusion limited
Thickening of alveolar capillary membrane
High altitude/Low FIO2
Increased pulmonary blood flow
34
Diffusion limited O2 transfer - thickening of capillary membrane
Increases time for diffusion across membrane
Decreases rate of diffusion
Sever pulmonary diseases - pulmonary fibrosis
35
Diffusion limited O2 transfer - Low FIO2/high altitude
Decreased alveolar O2 pressure and decreased gradient across alveolar membrane
Decreases rate of diffusion
36
Diffusion limited O2 transfer - Increased pulmonary blood flow
Increased cardiac output = blood moves rapidly through lung and complete saturation is not achieved
Diffusion is not fast enough to keep up with perfusion
37
Amount of dissolved O2 in 1L of blood
3mL at PO2 of 100mmHg
38
Majority of oxygen in blood is located where...?
Bound to Hb
~96%
39
1g of Hb contains how much O2 when 100% saturated
1.34mL
40
Hb saturation in lung vs tissues
Hb in lung is almost 100% saturated
Hb in tissue is \<60% saturated (O2 leaves Hb to go to tissue)
41
Left shift of HbO2 curve - causes and meaning
Hb has higher affinity for O2 at lower partial pressure
Decreased PC02
Increased pH (Decreased H)
Decreased temp
Decreased 2,3 BPG
42
HbO2 curve shifted to right - causes and meaning
Lower affinity to Hb given partial pressure of O2
Increase PCO2
Decrease pH
Increase temp
Increased 2,3 BPG
43
CO poisoning
Super high affinity to Hb, making it unavailable to carry Oxygen
When Hb binds to CO, P50 decreases and increases affinity for oxygen
Less oxygen carried and less oxygen released
44
Fetal hemoglobin
Higher affinity for O2
HbO2 shifted to left, decreased P50
Need to be able to take oxygen from placenta to fetus
45
Adequate delivery of oxygen to tissues requires:
Oxygen content in blood: Adequate PaO2 and hemoglobin
Cardiac output: Adequate delivery of oxygen to arteries
Vascular supply: Adequate delivery of oxygen to tissues
46
Hypoxemic hypoxia
Low PaO2 --\> low oxygen saturation of Hb
47
Anemic hypoxia
PaO2 is normal
Oxygen carrying capacity is low --\> low O2 content
Anemia
48
Circulatory hypoxia
Oxygen content normal
Blood flow to tissues reduced
Shock
49
Histotoxic hypoxia
Oxygen content and blood flow is normal
Tissue cannot use oxygen at cellular level
Cyanide poisoning
50
Carriers of CO2
Physical solution
Bicarbonate
Carbamino compounds (CO2 bound to NH4 on Hb)
51
Solubility of CO2
20x more solube than O2
.06mL CO2 dossolved/100mL blood per mmHg partial pressure
52
Major form of CO2 carried in blood
HCO3 in RBC
53
Deoxygenated Hb and Carbonic anhydrase equation
Deoxygenated hemoglobin accepts H+ --\> reduces H+ --\> drive reaction to HCO3
Tissues = deoxygenated Hb = H acceptance = CO2 pickup as HCO3
54
Oxygenated Hb and Carbonic anhydrase equation
Oxygenated Hb releases H+ and drives reaction towards CO2
Oxygenated Hb in lungs = released H+ = CO2 production
55
Difference between CO2 curve and O2 curve
Higher total content of CO2 in blood per mmHg partial presure
Steeper slope (more change in CO2 content per change in PCO2)
No effective plateau or max content
56
Haldane effect
As PO2 increases, CO2 dissociation curve shifts downward
Less CO2 carried in blood
Lungs: Blood takes up oxygen, CO2 released and expired
Tissues: Blood releases oxygen, increases capacity for CO2, takes up CO2 to transport ot lungs
57
Law of mass action and CO2: Lungs and tissue
Lung: PCO2 drop causes carbamino compounds and Bicarb to generate CO2 (In RBC)
Tissues: Increase in PCO2 forms HCO3 and carbamino compunds for transfer to lungs
58
RBC Carbonic anhydrase action in lungs
HCO3 decreases rapidly b/c forming H20 + CO2
Decrease in RBC HCO3 = HCO3 diffuses into cell = Cl exit from cell
59
RBC carbonic anhydrase in tissues
HCO3 rapidly increases inside RBC --\> diffuses out of cell --\> Cl entry
60
Ventilation/Perfusion (V/Q) ratio and CO2?O2 levels
Increased V/Q = increased ventilation = increased O2 and decreased CO2 (removal of CO2 and delivery of fresh O2)
Decreased V/Q = increased perfusion = decreased O2 and increased CO2 (Increased CO2 delivery with less O2, increased gas exchange)
61
V/Q at bottom/base of lung
Decreased V/Q
Perfusion higher than ventilation
Bottom of lung will have higher PCO2 and lower PAO2
62
V/Q at top/apex of lung
Increased
More ventilation relative to perfusion
Increased PAO2 and decreased PCO2
63
V/Q = infinity = ?
Highest amount of Oxygen and no CO2
Dead space, no perfusion, no gas exchange
64
V/Q = 0 = ?
No ventilation and complete perfusion
High CO2 and no O2
Shunt, blood does not get oxygenated
65
Compensatory response of hypoventilated part of lung
Other lung units can hyperventilate and lower CO2
Average all units CO2 to get CO2 of lungs
66
Compensatory O2 response of hypoventilated lung
Mixed blood O2 is NOT average of different units because hyperventilation of other units does not increase O2, saturation has already occurred
67
Central hypoventilation gas result and treatment
Central hypoventilation results in an increased PaCO2 which results in a decreased PAO2
Giving oxygen with an increased FIO2 can overcome this
68
Steps to find cause of hypoxemia
Calculate PAO2 and decide if hypoventilation is cause
If not hypoventilation --\> measure diffusion capacity to see if there is diffusion limitation
If not diffusion limitation --\> V/Q mismatch or shunt. Give oxygen: V/Q mismatch will resolve, R-\>L shunt will not
69
Tidal volume
Amount of air exchanged with each breath
~7.5L/min
70
Residual volume
Volume of gas left in lung after a complete expiration
Unable to completely empty lung because we cannot completely collapse chest
25% TLC
71
Inspiratory reserve volume
Volume of air that can be inspired from end of tidal inspiration to total lung capacity
Use if need to take deeper breath
72
Expiratory reserve volume
Volume of air we can exhale from end of tidal expiration
Forced exhale, dry cough
73
Total lung capacity
Total lung capacity
Volume at which inspiratory muscles are no longer strong enough to overcome expiratory recoil of lung and chest wall
74
Vital capacity
Volume of air that can be exhaled from TLC to RV
All volumes except RV
Measure by asking pt to inspire completely and expire into spirometer
75
Functional Residual capacity
Volume of gas in lungs at end of tidal expiration
Sum of ERV and RV
FRC prevent hypoxemia during exhalation
76
Inspiratory capacity
Complement of FRC
TLC = FRC + IC
Sum of TV + IRV
77
Non compliant lung
Require greater pressure change for each breath
Restrictive
78
Surfactant
Complex protein/phospholipid taht interrupts surface tension laws of lung
Low surface tension when area is small
High surface tension when surface area is large
Accounts for hysteresis in lung inflated with air
79
Surfactant and low/high volumes
Low volume inflation --\> surfactant is in water layer and not at surface, does not reduce surface tenstion
High volume inflation --\> surfactant spreads on surface and reduces surface tension
Lung more compliant at higher volume (inflated)
80
Pleural pressure gradient in lung
Occurs due to weight of lung
Top of lung: No weight added, pleural pressure at its most negative
Bottom of lung: Lung weight added and causes less negative pleural pressure
81
Pleural pressure gradient and alveoli
Alveoli at apex will be higher percent of max volume compared ot base of lung
82
Lung base: pleural pressure, alveolar volume
Pleural pressure is less negative
Alveoli at a lower volume
Alveoli are more compliant
83
Lung apex: Pleural pressure and alveolar volume
Pleural pressure is more negative
Alveoli at higher volume
Apex alveoli are less compliant
84
Pulmonary HTN definition
Resting mean pulmonary arterial pressure \>25mmHg
Normal is between 8 and 20mm Hg
85
Pulmonary arterial HTN (PAH) definition
Mean pulmonary arterial pressure \>25mm Hg
PUlmonary venous (pulmonary capillary wedge) pressure \<15
86
Group 1 PAH
Pulmonary arterial HTN
Idiopathic PAH
Inherited
Connective tissue disease, HIV, portal HTN, congenital heart disease
87
Group 2 Pulmonary HTN
Pulmonary HTN due to left heart disease
Systolic dysfunction
Diastolic dysfunction
Valvular disease
88
Group 3 Pulmonary HTN
Pulmonary HTN due to lung disease and/or hypoxia
COPD
Interstitial lung disease
Sleep disordered breathing
89
Group 4 pulmonary HTN
Chronic thromboembolic pulmonary HTN
CTEPH
90
Components of pulmonary pressures
Pulmonary venous pressure/LA pressure
Pulmonary vascular resistance
Right sided Cardiac Output
91
Causes of increased pulmonary venous pressure
Left ventricular or diastolic dysfunction
MItral valve disease
92
Causes of increased pulmonary vascular resistance
Conditions that decreases area of pulmonary vascular beds (pulmonary emboli, CT disease, interstitial lung disease, COPD)
Conditions that induce hypoxic vasoconstriction
93
Causes of increased right sided cardiac output
L--\>R ASD
L--\>R VSD
Other systemic --\> pulmonary shunts
Increases Right Ventricular volume
94
Pulmonary HTN sequence of events
Initiatl injury --\> mild P HTN --\> elevated pressure damages pulmonary vasculature --\> narrowed pulmonary vascular bed --\> RV hypertrophy to overcome increased resistance --\> vascular injury accelerates with increased pulmonary arterial pressure --\> increased RV afterload --\> RV failure
95
Genetic predisposition to PAH
Genetic mutations in bone morphogenetic protein receptor type 2
BMPR2
Inuces apoptosis in certain cell types
Permits excess endothelial cell grownt and proliferation in response to injury
96
Sigaling pathways disturbed in PAH
Decreased prostacyclin and decreased Nitric Oxide pathways --\> Inhibit vasodilation and increases proliferation
Increased endothelin pathway --\> Vasoconstriction and increased proliferation
97
Pulmonary HTN clinical presentation and physical exam
Dyspnea on exertion and fatigue
RV failure = ankle swelling
Exertional chest pain, syncope can develop
Increased intensity of pulmonic component of S2
98
Community acquired pneumonias
95% due to viral, mycoplasma, pneumococcal, or Leigonella infections
99
Nonsocomial pneumonias
1% of hospital patients
ICU patients at highest risk
G(-) bacilli
Staph Aureus
100
Aspiration pneumonias
Caused by aspiration of infective material and/or gastric contents
Anaerobic bacteria
Chemical pneumonitis, necrotizing pneumonia, lung abscess, empyema
101
Pneumonia in immunocompromised hosts
Suppressed immune system due to disease or drugs
Opportunistic organisms
102
Pathogenesis of pneumonia
Loss of defense mechanisms
1. Inhibition of normal cough reflex from NM disease, drug overdose, intubation, coma --\> allows gastric contents/oropharyngeal flora to aspirate into lungs
2. Injury of mucociliary apparatus prevents clearance of small inhale particles/microorganisms: Viral destruction, smoking, genetic disease
3. Interference of phagocytic or bactericidal action of alveolar macrophages - alcohol, tobacco smoke, snoacia
4. Bronchial obstruction - neoplasm, mucus plugging --\> prevents clearance
5. Decreased immunity
103
Alternative factors/mechanisms of pneumonia pathogenesis
Direct introduction of organisms into sterile lung by intubation/contaminated respiratory equipment
Hematogenous spread of infections
Bacteria common to hospital environments are often drug resistant
104
Bacterial pneumonia classification
Based on etiological agent and anatomic distribution pattern
105
Clinical presentation, PE, CXR of bacterial pneumonia
Malaise, fever, chills, pleuritic pain, productive cough (blood tinged)
Decreased breath sounds in affected lobes, expiratory rales
May have Leukocytosis with left shift
CXR - focal opacaties and occasionally pleural effusions
106
Most common organism causing pneumonia in ambulatory patients
Strep Pneumoniae
107
Most common cause of pneumonia in hospitalized patients
Gram(-) bacilli (Pseudomonas, Klebsiella, Proteus, E Coli)
Reach lungs via upper airways or through blood
108
Upper respiratory viral infections follwe dby...
Staphylococcal and Haemophilus
109
Legionella pneumophila
Associated with aerosols from cooling systems
Multiple small abscesses
Only grows on special media, may be missed on culture
110
Pathology: Bronchopneumonia
Lobular pneumonia
Gross: Patchy consolidation. Infiltrates associated with airways and represent extension of preexisting bronchitis/bronchiolitis
Microscopic: Alveolar spaces filled with suppurateive exudate composed of PMN, RBC, fibrin, edema, macrophages
Alveolar septa hyperemic and congested, not inflamed
111
Pathology: Lobar pneumonia
Gross/microscopic:
Consolidation by fibrinopurulent material is widespread and involves entire lobes/lobules
Rarely seen
112
Complications of bacterial pneumonia
1. Abscess
2. Empyema
3. Organization
4. Bacteremic dissemination
113
Complication of bacterial pneumonia: Abscess
Local suppurative process
Destruction of lung tissue and accumulation of neutrophils
Associated with aspiration, septic emboli, and bronchial obstruction
Strep Pneumoniae
114
Organism that most commonly causes abscess in pneumonia
Strep Pneumoniae, Pseudomonas aeruginosa, Staph aureus, anaerobes
Contain enzymes that liquify lung tissue
115
Complication of bacterial pneumonia: Empyema
Purulent inflammation of pleural space caused by spread of infection into pleural cavity
116
Complication of bacterial pneumonia: Organization
If fibrinous alveolar exudate is not broken down and reabsorbed --\> organization
Formation of intraalveolar plugs of granulation tissue composed of fibroblasts, fibrin, and inflammatory cells
Can mature into fibrous tissue --\> Scarring
117
Complication of bacterial pneumonia: Bacteremic dissemination
Sepsis
Spread to other organs
118
Viral pneumonias - more common in children or adults
Children
119
Clinical presentation of atypical pneumonias
Fever, headache, muscle aches
Dry, hacking, non productive cough
Most common complication is secondary bacterial pneumonia
120
Atypical pneumonia gross appearance
Discrete infiltrates, difficult to appreciate
Rare pleural effusions
121
Microscopic appearance of atypical pneumonias
Mononuclear interstitial inflammatory infiltrate within walls of alveoli
Alveolar septa widened and edematous, alveolar space may contain protein rich fluid
Type II pneumocytes are hyperplastic
Alveolar wals lined by hyaline membranes
122
Herpes, varicela, adenovirus atypical pneumonia microscopic appearance
Necrosis of bronchial and alveolar epithelium
123
CMV, herpes, and measles atypical pneumonia microscopic appearance
Viral inclusions within infected cells
124
Chronic Granulomatous infection categories
Fungal infections
TB
125
Pneumonial fungal infections
Coccidiomycosis
Histoplasmosis
Blastomycosis
126
Coccidiomycosis
Fungal infection caused by Coccidioides
Southwest US
Lung lesions, pleuritic pain, cough
Seen in tissue as large double walled spherules - filled with endospores
Granulomatous inflammation with giant cells and macrophages
127
Histoplasmosis
Fungal infection caused by Histoplasma
Central US
Usually asymptomatic until immunocompromised
128
Blastomycosis
Funcgal infection caused by Blastomyces
Eastern US
Granulomatous response
129
Tuberculosis
Mycobacterial infection caused by Mycobacterium tuberculosis
130
TB: Pattern of infection
Primary infection: Granulomas in lung and lymph nodes that frequently calcify
Secondary infection: Re activation. Usually in apices
Fibrocaseous disease: Upper lobe, cavities common
Miliary Spread: Hematogenous dissemination, innumerable micronodules in lungs, liver, spleen etc
Bronchopneumonia: Seen in overwhelming disease
131
TB clinical presentation
Primary infection - asymptomatic or flu like disease
Secondary infection - more severe symptoms
Erosion of lesions into blood vessels --\> hemoptysis
132
TB pathology
Caseating granuloas
Epithelioid histocytes surrounded by lymphocytes, fibroblasts, giant cells
Central caseous necrosis
133
Progressive pulmonary TB
Active lesions may continue to progress --\> cavitary fibrocaseous TB, miliary dissemination, TB bronchopneumonia
134
Opportunistic infections
Pneumocystis jiroveci
Aspergillus
Zygomycetes
Cryptococcus
Candida/torulopis
CMV, HSV
Actinomyces and Nocrdia
135
Pneumocystis jirovechi
Alveolar infiltrate of foamy material and mononuclear cells
Seen in HIV pts with CD4 \<200
136
Aspergillus
Ubiquitous fungal organism found in soil and inhaled into lungs
Colonize old cavities from previous disease and grow as fungus ball
Can invade parenchyma and produce necrotizing pneumonia
Invades arteries and veins --\> hemorrhagic infarcts
Septae hyphae branching @ 45 degree angle
137
Zygomycetes
Invade arteries and veins
Hyphae are pauciseptate and branch at 90 degree angle
138
Cryptococcus
Inhaled encapsulated yeast which causes mild pulmonary symptoms
Often spreads to CNS
Thick gelatinous capsule which appears as halo after tissue fixation
139
Candida and Torulopis
Produce bronchitis,bronchopneumonia, hemorrhagic pneumonia, acute abscesses
In immunicompromised patients
140
CMV and HSV
Hemorrhageic interstitial pneumonias
141
Actinomyces and nocardia
Filamentous branching bacteria which produce acute pneumonia with rapid progression to abscesses
142
FEV1/FVC less than LLN = ?
Obstructive defecit present
143
FVC less than LLN = ?
Restrictive deficit
144
Pulmonary circulation, pressure and resistance?
Low pressure, low resistance system
145
Gravity and pulmonary circulation
Apex: Low vascular pressure, collapsed vessels
Base: High vascular pressure, distended vessels
Interstitial pressure most negative at apex --\> alveolar pressure is greatest at apex --\> compresses vessels
146
Zone 1 of lung
Apex of lung
Palveoli \> Parterial \> Pvenous
No flow conditions, vessels collapsed shit
Alveolar dead space
147
Zone 2 of lung
Parterial \> Palveolar \> Pvenous
Arterial pressure is greater than alveolar so there is flow
148
Zone 3 of lung
Parterial \> Pvenous \> Palveolar
Continuous flow
Blood pressures at either end of system determine flow
Vessels completely distended
149
Extrapulmonary vessel distention at apex and base of lung
Apex: Fully distended b/c not exposed to alveolar pressure AND pleural pressure most negative
Base: Collapsed b/c pleural pressure least negative
150
Passive effects on pulmonary vascular resistance
1. Vascular pressures
2. lung volume
151
Vascular pressure effects on pulmonary vascular resistance
Increased vascular pressure = distended vessels = decreased resistance
152
Pulmonary vascular resistance during exercise
Increased CO = increased pulmonary artery pressure = Decreased pulmonary vascular resistance
1. Vessels distended = decreased resistance
2. Opening of closed (zone 1) vessels increases total cross sectional area = decreased resistance
153
Pulmonary vascular resistance during shock
Decreased cardiac output = decreased pulmonary vascular pressure = collapsed vessels = increased resistance
De-recruitment of upper zones due to drop in pressure and collapse of vessels
154
Lung volume and pulmonary vascular resistance
High lung volume: Intra-alveolar vessels = collapsed, extra-alveolar = distended
Low lung volume: Intra-alveolar vessels = distended, extra-alveolar vessels collapsed
155
Intra-alveolar vessels have lowers resistance at what volume
Residual volume (lowest volume)
156
Extra-alveolar vessels have lowest resistance at what volume
TLC, highest volume
157
Active regulation of pulmonary vascular resistance
1. Neural
2. Local
3. Humoral
158
Local control of pulmonary vascular resistance
1. Alveolar hypoxia causes vasoconstriction. Shunt blood to ventilated areas of blood
2. Acidosis, hypercapnia, and prior smooth muscle hypertrophy accentuate the hypoxic vasoconstrictive response
Pulmonary vascular resistance is highest when alveolar hypoxia occurs in the face of acidemia
159
Pulmonary edema types
Hydrostatic edema
Non hydrostatic edema
160
Hydrostatic edema
Pulmonary edema due to increased pulmonary capillary pressure
Fluid backup:
Mitral valve stenosis
LV failure
Fluid overload due to renal failure
161
Non hydrostatic pulmonary edema
Chemical/thermal injury: Chemical inhalation, drowning, smoke inhalation
Humoral and immune injury: Endotoxin, prolonged shock, head injury
162
Receptors that monitor effects of breathing
1. Chemoreceptors - respond to O2, CO2, and pH
2. Mechanoreceptors - Respond to mechanical information from respiratory pump
163
Dorsal Respiratory Group
Inspiration
Controls basic rhythm of breathing
Quiescence --\> crescendo of neuronal activity (inspriation) --\> quiescence (expiration occurs here)
Input from CN IX/X
Output via phrenic nerve to diaphragm and other outputs to chest wall/upper airway muscles
164
Ventral Respiratory group
Expiratory area is inactive during normal respiration (expiration is passive during quiet breathing)
Exercise/lung disease - Activity in these neurons for active expiration
165
The Apneustic Center
Lower pons
Brainstem damage above this area results in apneustic breathing --\> isolated from pneumotaxic center
Sends signals to DRG that prolong duration of excitatory ramping of diaphragm activity
166
Apneustic breathing
Prolonged inspiratory gasps with rapid expiration
167
Pneumotaxic Center
Upper pons
Responsible for ending inspiration, terminates inspiration activity
168
Central chemoreceptor
Primary chemical control of regular quiet breathing
Ventro-lateral medulla, close contact with CSF
Increased CO2 = increased ventilation
Chemoreceptor senses H+ difference (carbonic anhydrase equation)
169
Peripheral chemoreceptor locations and respond to ?
Carotid and aortic bodies
Respond to:
1. Decreased PaO2
2. Increased PaCO2
3. Increased H+ (decreased pH)
170
Ventilatory response to hypoxia
Increase in peripheral chemoreceptor activity with PaO2 less than 500
NON LINEAR RESPONSE
Minimal increase until PaO2 less than 100
Dramatic increase when PaO2 less than 60
171
Pulmonary stretch receptors
Slowly adapting receptors that respond to stretching of airways
Transmit information via vagus
Responsible for vagal mediated inhibition of inspiration and promotion of expiration
172
Pulmonary irritant receptors
Extra-pulmonary airway epithelium
Rapidly adapting
Under conditions of continued irritation --\> adapt and reduce activity
Respond to:
1. Chemical irritation: Gas, antigens, inflammatory mediators
2. Physical irritation: Airflow, particulates, bronchial smooth muscle tone
3. Lung volume: Initiate sighs to maintain lung volume
173
Juxtacapillary Receptors
Located in alveolar walls near capillaries
Connect to central controllers via unmyelinated fibers, rapidly adapting
Stimulated by interstitial edema, inflammation
Also stimulated by increased left atrial and pulmonary venous pressure
Cause laryngeal closure and apnea, followed by shallow rapid breathing
174
Chest wall proprioceptors
1. joint receptors
2. Tendon receptors
3. Muscle spindle receptors
175
Joint receptors
Ruffini, pacinian, golgi organs
Activity proportional to rate of rib movement
176
Tendon organs
PResent in intercostal and diaphragm muscle tendons
Monitor force fo contraction and inhibit inspiration
177
Muscle spindle receptors
Abundant in intercostals, rare in diaphragm
Stabalize rib cage and compensate for changes in body positions
Passive stretch --\> increase afferent activity --\> stimulate alpha motor neuron --\> contract intercostal muscle
178
Respiratory control failure and disease states: Increased work of breathing
Obstructive diseases: COPD, obesity, sleep apnea
Causes response to CO2 to be blunted --\> rise in CO2
Due to down regulation of response system due to maximum amount of work level reached
179
Respiratory control failure and disease states: Decreased efficiency of gas exchange
More work needed to achieve same result
Can lead ot diminished ventilatory drive
180
Respiratory control failure and disease states: Impaired ventilatory pump performance
Hyperinflation due to obstruction stretches inspiratory muscles and they become inefficient
Chest wall restriction (muscular dystrophy) also decreased ventilatory response
181
Respiratory control failure and disease states: Chronic CO2 retention
Leads to bicarb reabsorption in kidney causing metabolic alkalosis
Bicarb enters CSF over time and buffers change in H normally associated with CO2 increase
Abolishes central chemoreceptor drive
182
CFTR gene and mutation
DF508
Deletion of Phenylalanine at 508 position
183
CFTR protein
ATP binding anion channel
184
Pathophysiology of CF respiratory disease
Mucociliary clearance dysrupted due to inadequate hydration of airway surface liquid
Increased activity of ENaC --\> Cl entry via electrochemical gradient --\> water entry into cell --\> decreased airway surface liquid
No mucociliary clearance = higher risk of infection, inflammation, obstruction --\> chronic lung disease
185
Most common infective organism in CF
Pseudomonas
Staph aureus
186
CF is what type of lung disease?
Obstructive
187
Pathophysiology of CF GI disease: exocrine
Exocrine pancreatic insufficiency:
Autodigestion of pancreas w/ fibrosis, cysts, fatty replacement --\> no enzyme production
--\> Maldigestion of fats/proteins
Can cause bowel obstruction
188
Pathophysiology of CF GI disease: Other
CF Diabetes mellitus
Hepatobiliary disease: Inadequate bile flow, altered bile salts, inadequate bicarb concentration in bile --\> Cholelithiasis, cholecystitis, biliary cirrhosis + portal HTN
GERD: Lung hyperinflation + reduced GI motility
189
Pathophysiology of CF genitourinary disease
Male infertility: Absence of vas deferens secondary to blockage/inflammation/fibrosis
Female reduced infertility: Failure of normal thinning of cervical mucus at ovulation
Nephrolithiasis: 5%
190
CF salt loss in sweat
Normal sweat physiology: As sweat moves up duct, Na absorbed and Cl follows
CF sweat physiology: High sweat Cl values b/c Cl not reabsorbed
Increased Cl loss can lead to dehydration and metabolic alkalosis
191
CF Sweat Test
Pilocarpine Iontophoresis
192
Neonatal CF presentation
Meconium ileus
Prolonged jaundice (slow bile clearance)
193
Positive newborn screen for CF
Immunoreactive trypsinogen elecated
If elevated then do genetic testing
Sweat testing
194
CF presentation in infancy
Respiratory disease: Persistent wheezing/coughing, opacities on CXR, Staph pneumonia
Failure to thrive due to pancreatic insufficiency
Malabsorption/steatorrhea
Fat soluble (ADEK) vitamin deficiency (pancreatic insufficiency)
Metabolic alkalosis (Cl loss)
195
CF presentation in childhood
Same as infancy
Greater risk for bronchiectasis/chronic sputum, digital clubbing, and airway obstruction on PFT
Rectal prolapse
Distal intestinal obstruction syndrome (thick dry stool)
Liver disease
Chronic/recurrent pancreatitis
Nasal polyps and sinusitis
196
CF adolescence/adulthood presentation
Greater risk of advanced lung disease
Chronic pansinusitis
Bronchiectasis complications - pneumothorax/hemooptysis
More advanced liver disease
Azoospermia
197
CF Diagnosis
One or more clinical features
+
Two CF mutations OR Two positive sweat tests OR abnormal nasal potential difference
198
CF treatment categories
Lung treatment
Chest clearance
Anti infective
Anti inflammatory
Pulmonary exacerbations
Lung transplant
Chronic sinusitis
199
CF treatment - Chest clearance
1. Chest physiotherapy w/manual chest compression
2. Bronchodilator
3. Aerosolized hypertonic saline - Increase water, stimulate cough, shrink mucosa or airways
4. Dornase alfa - Recombinant DNAse that breaks up DNA in sputum which liquefies it
5. Exercise
200
CF treatment - anti infective
Inhaled, Oral, IV antibiotics
Anti fungal
Anti mycobacterial
201
CF treatment - Pulmonary exacerbations
Increased lung symptoms, loss of function, weight loss
Comprehensive therapy: IV antibiotics, chest clearance, nutrition, anti inflamm
202
CF treatment - anti infective
Inhaled antibiotics - Psudomonas
Oral - Pseudomonas, Staph (mild exacerbations)
IV - Treat exacerbations
Anti fungal - aspergillus
Anti mycobacterial
203
CF nutritional treatment
Good nutrition is essential
High calorie, high fat
Salt supplementation in infants
204
CF enzyme replacement
Replace pancreatic enzymes
205
Asthma definition
Chronic inflammatory disorder of airways
Mast cells, eosinophils, T cells, macrophages, PMN, epithelial cells
Bronchial hyper-responsiveness to normal stimuli
206
Classic asthma pathogenesis
Th2 cell dependent, IgE mediated allergic disease
CD4 T cells, mast cells, eosinophils
Typical TH2 cytokines (IL-13, IL-4, IL-5)
207
Asthma hygeine hypothesis
Increased hygiene and cleanliness reduces proper immune system development via environmental cues
Normally immune system shifted away from Th2 response
208
Asthma triggers
Allergens
Infections
Exercise
Cold air
Air pollution
Cigarette smoke
Beta Blockers/NSAIDs
Emotions
209
Clinical presentation for asthma diagnosis
Wheeze
Cough
Dyspnea
Chest tightness
Worse symptoms at night
210
Chest exam during acute asthma attack
Expiratory wheezing
Hyperinflation
Prolonged expiratory time
211
Early response of airway to asthma
Bronchospasm
Edema
Airflow obstruction
212
Late response of respiratory system to asthma
Airway inflammation
Airflow obstruction
Airway hyper-responsiveness
213
COPD definition
Airflow limitation that is not fully reversible
Progressive and associated with abnormal inflammatory response of lungs to noxious particles/gases primarily caused by cigarette smoking
214
Obstructive lung disease - bronchospasm
Asthma
215
Obstructive lung disease - destruction of alveolar walls
Emphysema
216
Obstrucive lung disease - small airways abnormalities
Chronic obstructive bronchitis
217
Genetic cause of emphysema
Alpha-1 Antitrypsin Deficiency
SERPINA1 gene
Protease inhibitor that protects lung from neutrophil elastase and neutrophil mediated destruction
218
Severity measurement of COPD
Level of FEV1 decrease
219
Categories of obstructive lung disease drugs
Bronchodilators
Anti inflammatory agents
220
Bronchodilator categories
Beta agonists
Anti cholinergics
Theophylline
221
Anti inflammatory agent categories
Corticosteroids
Comolyn/Nedocromil
Leukotriene inhibitors
222
Beta agonist overview
Most effective bronchodilators for asthma
Antagonize bronchosconstriction in airways of all sizes
Short acting so helpful for acute dyspnea and wheezing episodes
223
Route of administration for Beta agonists
Inhalation
Decreases plasma concentration and reduces side effects
More rapid and effective
224
Beta agonist adverse effects
Tremor - skeletal muscle stimulation
Palpiatation - Peripheral vascular vasodilation --\> cardiac response
Hypokalemia in high doses
225
Anti Cholinergics
Atropine use is limited by side effects
Tachycardia, blurred vision, dry mouth, urinary retention
226
Ipratropium
Anticholinergic
Poorly absorbed into systemic circulation and produces no significant side effects
227
Anti cholinergic MoA
Bronchodilation by anatagonizing ACh on M receptors in airway smooth muscle
228
Tiotropium
Long duration of action and is used for COPD
229
Theophylline
Second line therapy for asthma and COPD
Unclear MoA but, smooth muscle relaxation, improved diaphragmatic contraction, increased mucociliary clearance
230
Theophylline pharmacokinetics
Metabolized by cytochrome system in liver
Affected by inhibtors/inducers of Cytochromes
231
Theophylline toxicites/adverse effects
Nausea, tremor, headache, agitation, insomnia
Severe toxic effects at high doses - seizures and arrhythmias
232
Theophylline indications
Second line therapy
Only after failure of primary drugs
233
Corticosteroids
Bind to GR and prevent downstream effects ie inflammation
234
Adverse effects of corticosteroids
General - Cushingoid, immune suppression, infection
Endocrine - Adrenal insufficiency, glucose intolerance
MSK - Osteoporosis/compression fractures, myopathy
Ophto - Cataracts, glaucoma
CV - HTN
Psych - Psychosis
GI - Pancreatitis
Cutaneous - Purpura, delayed wound healing
235
Inhaled corticosteroids
Reduce symptoms, improve lung function, decrease bronchial hyperresponsiveness compared to inhaled B2 agonists
236
Pharmacokinetics of inhaled corticosteroids
80-90% of inhaled drug and deposited in oropharynx and swallowed
Absorbed and causes systemic effects
10-20% reaches respiratory tract
237
Inhaled corticosteroid drugs
Beclomethasone
Budesonide
Fluticasone
Mometasone
238
Adverse effects of inhaled corticosteroids
Oropharyngeal candidiasis (high doses)
Dysphonia (myopathy of laryngeal muscles)
Slow growth in children
239
Indications for corticosteroids
Most effective for treatment of acute exacerbations and chronic asthma
Inhaled corticsteroids are first line therapy for chronic asthma
Systemic corticosteroids are used for acute exacerbations of COPD
Chronic COPD - documented improvement with steroids or patients with severe COPD and repeated exacerbations
240
Cromolyn sodium and nedocromil sodium
Anti inflammatory effects and improve bronchial hyperresponsiveness with chronic therapy
Protect against bronchoconstrictive stimuli (exercise)
241
Cromolyn sodium and nedocromil sodium administration and side effects
Inhaled
No important side effects
242
Leukotriene inhibitors
Prevent synthesis and action of leukotrienes
Block receptors OR block 5-lipooxygenase so no synthesis
Montelukast
Oral administration
243
Asthma treatment
Step wise approach
All start with short acting Beta2 agonist for as needed
If not controlled then "controller agent" added - low dose inhaled corticosteroid
244
Acute severe asthma exacerbation treatment
Inhaled short acting B2 agonist
Systemic corticosteroid therapy
245
COPD treatment
Bronchodilator medications are most important: B2 agonists, anti cholinergic, theophylline
Prolonged inhaled corticosteroid treatment does not modify long term lung damage
246
Acute COPD exacerbation treatment
Inhaled B2 agonist
Inhaled anti cholinergic
Systemic corticosteroid
247
Etiologies of rhinitis
Allergic rhinitis - IgE mediated inflammation
Acute viral rhinitis - common cold
Non allergic noninfectious rhinitis - vasomotor rhinitis
248
Classes of drugs for rhinitis
Decongestants
Antihistamines
Cromolyn
Corticosteroids
Anti cholinergics
Leukotriene inhibitors
249
Decongestants
Alpha adrenergic receptor agonists
Produce vasoconstriction and decreases nasal congestion and blockage
250
Decongestant adverse effects and contraindications
Restlessness and insomnia
Elevated BP
Urinary retention
USE WITH CAUTION: HTN, BPH, MAO inhibitors
251
Topical decongestants
Repeated use leads to rebound congestion
Prolonged use may lead to chronic rhinitis, secondary hyperemia, tachyphylaxis, nasal mucosal irritability
Rhinitis Medicamentosa
252
Antihistamines
HIstamine normally causes smooth muscle contractin, increased capillary permeability, glandular secretion
H1 antagonists selective for H1 only
253
First generation H1 antagonists
Block muscarinic receptors producing anticholinergic side effecs
Also block H1 in CNS causing sedation
254
Second generation H1 antagonists
More selective, no muscarinic side effects, poor BBB crossing
No sedation
255
H1 antagonist symptom relief
Sneezing
Pruritis
Rhinorrhea
Less effective at relieving nasal blockade
256
Cromolyn sodium and nedocromil sodium for rhinitis
Inhibit antigen induced release of histamine from mast cells
Maximal efficacy when used prophylactically before episodic allergen exposure
257
Corticosteroids and rhinitis
Extremely effective in allergic rhinitis
258
Anti cholinergics and rhinitis
Submucosal glands rich in parasympathetic innervation
Ach release --\> nasal discharge
Anti cholinergics prevent nasal secretions
259
Decongestant symptom relief
ONLY NASAL BLOCKAGE
260
Cromolyn rhinitis symptoms relief
All, but not as effective as corticosteroids
Pruritis, blockage, sneezing, rhinorrhea
261
Corticosteroid rhinitis symptom relief
Very effective at relieving all
Pruritis, sneezing, rhinorrhea, nasal blockage
262
Anticholinergic rhinitis symptom relief
Effective and reducing rhinorrhea
263
Clinical aspects of COPD
Non specific symptoms - sometimes cough/sputum.
Dyspnea
Slowing of forced expiration
264
Emphysema definiton
Abnormal, permanent enlargement of air spaces distal to terminal bronchiole
Destruction of alveolar walls without obvious fibrosis
Natural elastic recoil (closing) of lung during exhalation is reduced because of destroyed lung tissue
265
Types of emphysema
Centracinar
Paracinar
266
Centracinar emphysema
Destruction of alveolar walls accentuated in center of acinus
Dilated air spaces
Microscopic - Round lesions, thin walls w/normal septa thickness but less protruding septa
20x more common
267
Panacinar emphysema
Destruction of alveolar walls that is diffuse, entire acinus and thus entire lobule
Alpha 1 antitrypsin deficiency
All air spaces enalrged
Microscopic - Lesions have smooth thin walls without protruding septa
268
Bulla
Emphysems lesion greater than 1cm
Usually subpleural
Can coexist with other epmysema or on its own
269
Paraseptal emphysema
Distal acinus
Sub pleural lung zones
Rare, can cause spontaneous pneumothorax
270
Protease-antiprotease emphysema pathogenesis
a1-AT neutralizes neutrophil elastase
Genetic defect can cause this
Smokers - Imbalance of proteinase and antiproteinase activity secondary to smoking
Smokers have more neutrophils in lung due to irritation, smoke inhibits a1-AT
271
Chronic bronchitis definition
Chronic inflammation of airways (small ones)
Fibrosis, chronic inflammation, muscular hypertrophy, pigment accumulation, mucous plugging, epithelial abnormalities
Caused by smoking
272
Simple chronic bronchitis
Involves large cartilaginous airways (bronchi)
Chronic cough and mucous production
Microscopic - chronic inflammation and enlarged bronchial mucous glands
Does NOT lead to rogressive disabling obstructive disease
Associated with more frequent infectious bronchitis
273
Extrinsic Asthma
Type I hypersensitivity reaction to environmental allergen --\> IgE coated mast cells bind --\> release histamine, Ach, cytokines, leukotrienes
Late phase reaction: PMN recruited to irritated ariways, eosinophils damage epithelium --\> bronchoconstriction
Can be familial: allergic rhinitis, eczema, urticaria
Drug induced and occupational asthma
274
Intrinsic asthma
Triggered by viral infections
IgE elevated
More common in adults
275
Gross and microscopic path of asthma
Gross: Obstructive mucous plugging, hyperinflation
Microscopic:
BM thickening and collagen deposition
Eosinophilic infiltrate
Mucous plugging
Variable smooth msucle enlargement, bronchial gland enlargement, chronic inflammation
276
Complications of asthma
All uncommon
Sudden death
Pulmonary HTN
Bronchiectasis (abnormal, permanent dilation of bronchi)
277
Obstructive disease PFT
TLC: Normal/high
FVC: Normal/low
FEV1: Low
FEV1/FVC: Low
278
Major physiological features of COPD
Airflow limitation
Hypoxemia
CO2 retention
279
Centracinar emphysema
280
Centracinar emphysema
281
Centracinar emphysema
282
Centracinar emphysema
283
Panacinar emphysema
284
Panacinar emphysema
285
Panacinar emphysema
286
Panacinar emphysema
287
Panacinar emphysema
288
Panacinar emphysema vs normal
289
Distal acinar emphysema
290
Distal acinar emphysema
291
Bullae
292
Chronic bronchitis w/ mucous plug
293
Normal airway wall
294
Chronic bronchitis
Increased mucous and inflammation
295
Small airways disease
296
Obstruction of small airwats in chronic bronchitis vs emphysema
Chronic bronchitis: INTRINSIC. Fibrosis, mucous plugging, inflammation
Emphysema: EXTRINSIC. Collapse of small airways in expiration due to lack of support
297
Asthma
298
Asthma
299
Asthma
Eosinophils
300
Acute Lung injury characteristics
1. Abrupt decline in respiratory function
2. Bilateral infiltrates
3. Reduced lung compliance
4. hypoxemia
5. Absence of heart failure
301
Acute lung injury causes
Caused by agents that diffusely injure lung parenchyma
Sepsis, aspiration, infection, trauma, radiation, inhalation of toxins, drugs
302
ARDS definition
Clinical syndrome characterized by sever acute respiratory failure
Manifestation of severe ALI
303
4 common causes of ALI and ARDS
Sepsis
Diffuse infections
Aspiration
Trauma
304
Diffuse alveolar damage definition
Pathalogical term
Histological manifestation of severe ALI, generally in association with clinical ARDS
305
Gross and microscopic path of DAD
Gross: Heavy, diffusely firm, red-tan lungs
Microscopic:
DIffuse damage to all parts of alveolar wall, including epi and endothelial injury
Hyaline membrane formation on surface of damaged alveoli
Hyperplasia of type II pneumocytes
Granulation tissue formation w/ influx of lymphocytes, macrophages, fibroblasts
306
Pathogenesis of DAD
Endothelial injury w/ endothelial activation
Recruitment of neutrophils
Accumulation of fluid in alveolar spaces
Hyaline membrane formation
Cytokine release that perpetuates inflammatory response
307
Treatment of ALI/ARDS
No proven treatments
Mechanical ventilation and supportive care
308
Prognosis of ALI/ARDS
40-50% recover
Many die acutely
Few develop diffuse fibrosis and die in weeks-months
309
Restrictive lung disease definition and settings
Characterized by reduced expansion of lung parenchyma
1. Diffuse diseases of interstitium (pulmonary fibrosis)
2. Chest wall disease w/ normal lungs (obesity, pleural disease, NM disease)
Results in DECREASED lung volume but airflow is normal or proportionally reduced
310
Categories of restrictive lung disease
Fibrosis disease
Granulomatous disease
Eosinophilic disease
Smoking related disease
Miscellaneous
311
Fibrosing idiopathic lung diseases
Idiopathic pulmonary fibrosis
Nonspecific interstiail pneumonia
Cryptogenic organizing pneumonia
Connective tissue disease associated interstitial lung disease
Drug reactions
312
Granulomatous restrictive lung diseases
Sarcoidosis
Hypersensitivity pneumonitis
313
Smoking related restrictive lung diseases
Desquamative interstitial pneumonia
Respiratory bronchiolitis associated interstitial lung disease
314
Miscellaneous restrictive lung diseases
Pulmonary alveolar proteinosis
315
Idiopathic pulmonary fibrosis definition
Clinical syndrome characterized by progressive interstitial fibrosis of lungs and respiratory failure
Associated with path pattern "usual interstitial pneumonia"
316
Usual interstitial pneumonia
Pathalogical pattern of fibrosis
Heterogenous and peripherally accentuated fibrosis
317
Clinical characteristics of IPF
Fibrosis only involves lungs
Smoking and metal fumes, wood dust increase risk
Prognosis worse than for all other types of chronic interstitial lung disease
318
Pathogenesis of IPF
Unknown cause but immune related
Unregulated fibrosis
Mediators released --\> fibroblast recruitment
319
Gross and microscopic path of IPF (UIP pattern)
Gross: Small lungs, diffusely bumpy pleura, fibrous tissue in peripheral lung zones, dilated air spaces surrounded by dense fibrous tissue (honeycombing)
Microscopic:
Patchy destruction of lung architecture, accentuated in periphery of lobules
Dense mature fibrosis adjacent to foci of new fibrosis with proliferating fibroblasts
320
Non specific interstitial pneumonia (NSIP) definition and characteristics
Chronic fibrosing interstitial lung disease that lacks characteristics of well characterized diseases
Diffuse homogenous thickening of alveolar walls by lymphocytes and fibrosis
Better prognosis
321
Cryptogenic organizing pneumonia (COP) definition and characteristics
Unknown cause
Injury to lung that results in filling of alveoli and terminal bronchioles by plugs of proliferating fibroblasts
Good prognosis b/c no mature fibrosis
Steroids to treat
322
Connective tissue disease associated ILD
CT disease if uncontrolled can cause lung fibrosis
RA
Scleroderma
Polymyositis
Sjogren
323
Drug induced lung disease
Disease caused by drugs, esp antineoplastic drugs
Look like DAD, UIP, NSIP
324
Sarcoidosis definition and characteristics
Multisystem granulomatous disease
Granulomatous inflammation and fibrosis
Lung involved in 90%
Non necrotizing granulomas distributed along lymphatic routes
CD4 T cells in lesions
325
Hypersensitivity pneumonitis definition
Acute/chronic interstitial lung diseases caused by heightened sensitivity and inappropriate inflammatory reaction to inhaled antigens
Reversible, lack mature fibrosis
326
Farmers lung
Spores of thermophilic bacteria in newly harvested hay
327
Pigeon breeder lung
Proteins from serum, droppings, bird feathers
328
Humidifier lung
Thermophilic bacteria in heated water resevoirs
329
Clinical features of HP
Symptoms related to antigen exposure
Fever, dyspnea, cough, leukocytosis
Pulmonary infiltrates
330
Path features of HP
Lymphoplasmacytic interstitial infiltrate in lungs
Small non necrotizing granulomas around airways
Chronic bronchiolitis
331
Desquamative interstitial pneumonia definition and characteristics
Smoking related interstitial lung disease
Accummulation of many macrophages within alveolar spaces, mild interstitial fibrosis
Chronic dyspnea, dry cough, clubbing of digits
332
Respiratory bronchiolitis associated interstitial lung disease
Smoking related interstitial lung disease
Milder than DIP, less macrophages
333
Pulmonary alveolar proteinosis definition
Rare disease caused by accumulation of surfactant within alveolar spaces and bronchioles
Defect in Macrophage function or granulocyte-macrophage-colony-stimulating factor (GM-CSF)
334
Types of PAP
Autoimmune: 90%. Anti GM-CSF autoantibody that neutralizes GM-CSF, alveolar macrophages cannot catabolize surfactant
Secondary: Caused by conditions that impair macrophage function
Hereditary: Mutations that disrupt GM-CSF
No chronic fibrosis
1/3 patient good, 1/3 bad, 1/3 same
Secondary infections can occur
Whole lung lavage
335
Intersitial disease
336
PFT in restrictive lung diseases
TLC: Low
FVC: Low
FEV1: Low
FEV1/FVC: Normal/high
337
Diffuse Alveolar Damage
338
DAD
hyaline membranes
339
Organizing DAD
340
Non spcific interstitial pneumonia
341
Sarcoidosis
342
Sarcoidosis
343
Desquamative Intersitial Pneumonia
344
Organizing pneumonia
Note spared lung and airspace filling
345
Organizing pneumonia
346
Hypersensitivity pneumonitis
347
Hypersensitivity pneumonitis
Note poorly formed non necrotizing granuloma
348
Hemorrhage
349
Capillaritis
350
Idiopathic hemosiderosis
351
Pulmonary alveolar proteinosis
352
Major types of primary neoplasms in lung
Carcinomas
Carcinoid tumors
Other
353
Lung cancer demographics
3rd most common cancer, leading cause of cancer death
Age 40-70
5 year survival is 15%
354
Major etiology of lung carcinomas
Smoking
355
Modern classification of lung carcinomas
Small cell
Squamous cell
Adenocarcinoma
Large cell
Other
356
Histological distinctions of lung cancer that change treatment
Small cell vs non small cell
Adenocarcinoma vs squamous cell
357
Gross appearance of primary lung cancer
Originate in large bronchi - Hilar (squamous or small cell)
* Firm infiltrating sold gray-tan mass in intimate association with large bronchus
Peripheral lung cancers - Adenocarcinomas
358
Small cell carcinoma histopathology
Invasive sheets or nests of small undifferentiated malignant epithelial cells
Contain chromatin but no prominent nucleoli, little cytoplasm
Originate from bronchial neuroendocrine cells
359
Squamous cell carcinoma histopathology
Invasive sheets, nests, cords of large malignant epithelial cells w/ intercellular bridges and/or keratin pearls
360
Adenocarcinoma histopathology
Large malignant epithelial cells forming invasive glandular structures
Adenocarcinoma in situ is slow growing, low grade variant - Large malignant cuboidal/columnar cells that grow across alveolar septal surfaces. Do not invade interstitium
361
Large cell carcinoma histopathology
Invasive sheets of large, undifferentiated malignant epithelial cells
No squamous or glandular differentiation
362
Complications of hilar tumor
Localized hyperinflation dur to partial bronchial obstruction
Atelectasis due to total bronchial obstruction
Bronchiectasis due to obstruction and inflammation
Post obstructive abscesses/pneumonia
Superior vena caval syndrome: Obstruction or SVC --\> engorgement of veins in head and arms
363
Complications of peripheral tumor
Pleural invastion and dissemination
Pleuritis and effusion
Invasion of vervical sympathetic plexus --\> horners syndrome (Pancoast Tumors)
364
Clinical course and prognosis of lung cancers
Cough, weight loss, chest pain, dyspnea
3/4 are unresectable at time of detection
365
Carcinoid Tumor
Low grade malignant neoplasm derived from neuroendocrine cells
NOT CAUSED BY SMOKING
Locally invasive, most do not metastasize
Surgery
366
Harmatoma
Benign mesenchymal neoplasm
Single, well circumscribed, spherical, peripheral lung nodule
Mature cartilage w/ other mesenchymal elements (fat, SM)
367
Hematogenous metastasis
Carcinomas arising in other anatomic sites can spread to lung via vasculature
368
Lymphangitic carcinomatosis
Invasion of lung via lympnatics
Linear, streaky tumor deposits
369
Hematogenous metastasis to large airways
Carcinoma from body can spread to lung and involve large airway
Mimick primary lung cancer
370
Aerogenous spread
Cancer that fragments off into aveoli and spread through airways to other parts of lung during breathing
371
Pleaural metastasis
Carcinoma spread to pleural surface and dissemination through pleural space
Effusion with malignant cells
Poor prognosis
372
Diffuse malignant mesothelioma
Malignant neoplasm arising from mesothelial lining of parietal or visceral pleura
Thick tumor rind that covers lung surface and inside of chest wall
Asbestos
Gland like/papillary structures
Spindle cells
Both
373
Small cell carcinoma treatment method
Chemosensitive
Not treated surgically
374
Non small cell carcinoma treatment option
Chemoresistant
Treat with surgery
375
Invasive adenocarcinoma
376
Invasive gland forming adenocarcinoma
377
Adenocarcinoma in situ at periphery of invasive adenocarcinoma
378
Adenocarcinoma in situ
379
Mucinous adenocarcinoma
Invasive
Can present as lobar consolidation
Grows along alveolar septa and as invasive papillae
Cells contain abundant mucin
380
Mucinous adenocarcinoma
381
Mucinous adenocarcinoma
382
Mucinous adenocarcinoma
383
Adenocarcinoma in situ origin
Bronchiolar (goblet/Clara) cell or Type II pneumocyte
384
Squamous cell carcinoma arise through sequence
Squamous metaplasia --\> squamous dysplasia --\> squamous cell carcinoma in situ --\> invasive squamous cell carcinoma
385
Squamous cell carcinoma
Central location
386
Squamous cell carcinoma
Cavitation
387
Squamous cell carcinoma
Keratin pearls
388
Squamous cell carcinoma intercellular bridges
389
Squamous metaplasia
390
Invasive squamous cell carcinoma
391
Large cell carcinoma
392
Small cell carcinoma
393
Small cell carcinoma
394
Small cell carcinoma
395
Types of Acute Respiratory Failure
Type I: Hypoxemic
Type II: Hypercapnic
396
Causes of hypoxemic respiratory failure
Pneumonia
Cardiogenic pulmonary edema
Non cardiogenic pulmonary edema (ARDS)
397
Causes of hypoxemia
V/Q mismatch
Shunt
Hypoventilation
Diffusion abnormalities
398
Causes of hypercapnic respiratory failure
CNS depression
NM disease
Chest wall abnormalities
Upper airway obstruction
Obstructive lung disease
399
Decreased alveolar ventilation = ?
Increased phsyiological dead space
Increased arterial CO2
400
Pneumoconiosis definition
DIffuse interstitial lung disease caused by inhalation of inorganic dust
Asbestos, Beryllium, Coal, Silica
401
Factors influencing pneumoiconosis development
1. Amount of dust retained in lung
2. Size and shape of particles
3. Solubility and chemical reactivity of dust particles
4. Presence of other irritants (cigarettes) or other disease
402
Defense mechanisms of respiratory tract
Filtration and impaction in upper respiratory tract
Cough
Mucociliary transport
Phagocytosis and transport by macrophages
403
Coal Workers Pneumconiosis definition and pathogenesis
Chronic lung disease caused by accumulation of inhaled coal dust
Poorly understood pathogenesis, fibrosis plays role
404
Simple CWP
Small aggregates of coal dust-laden macrophages form in terminal bronchioles/respiratory ducts
1. Little or not disturbance in ventilatory function
2. Little to no fibrosis
3. Associated with centracinar emphysema
4. May progress to fibrous nodules
405
Complicated CWP
Progressive massive fibrosis
Bulky fibrous nidules
Severe pulmonary symptoms and cor pulmonale
TB susceptible
406
Silicosis definition and pathogenesis
Inhaled silica dust in lung, fibrosis
Macrophage plays pivotal role in development of fibrosis
Silica interact with membranes --\> free radicals --\> enzymes and inflammatory cells recruited
407
Nodilar silicosis
1-5mm silicotic nodules, layers of acelular fibrous tissue and silica crystals
Lymph node involvement
Few symptoms
408
Complicated (Conglomerate) Silicosis
Coaslescence of smaler silica nodules into large fibrous masses
Respiratory impairment, R HF, severe symptoms
TB infection increased risk
409
Types of asbestos
Serpentine (white) asbestos
Amphibole (brown) asbestos
410
Pathogenesis of asbestos related diseases
Inhaled deep into lung because of narrow shape
Coated with iron and proteins --\> asbestos bodies
Lung parenchyma injured because of relseased chemical mediators when asbestos fibers phagocytized
411
Asbestosis
Diffuse interstitial fibrosis of lungs
NO fibrous nodules or masses, diffuse fibrosis instead
412
Asbestos pleural plaques
Thick deposits of fibrous tissue on surface of parietal pleura
No asbestos bodies!!
Marker for asbestos exposure, not specific though
413
Asbestos and cancer
Increased risk for diffuse malignant mesothelioma, lung carcinoma, other cancers
414
Latency of asbestos disease - carcinoma
Lung carcinoma develops in patients that are chronically exposed to large amounts
Several years before carcinoma
415
Latency of asbestos - pleural mesothelioma
25-40 years after asbestos exposure
Initial exposure can be short
416
Berylliosis definition
Accumulation of inhaled beryllium in lung
Variable degrees of granulomatous inflammation
417
Simple CWP
418
Progressive Massive Fibrosis
Complicated CWP
419
Silicosis
420
Silicotic nodule
421
Asbestos bodies
422
Pleural PLaque
423
Diffuse malignant mesothelioma
424
Granuloma in berylliosis
425
Carcinoid tumor - endobronchial mass
426
Carcinoid tumor
Nested growth pattern
427
Carcinoid tumor
Regular nuclei
Salt and pepper chromatin
428
Harmatoma
429
Harmatoma
430
Metastasis
Cannonball pattern
431
Lymphangitic carcinomatosis
432
Treatment summary: Non small summary
Stages I & II: Surgery
Stage III: Chemo/radiotherapy
Stage IV: Chemo vs targeted if adenocarcinoma has mutations
433
Squamous cell carcinoma
Central
434
Small cell carcinoma
Central location
Obstruct hilar vessels and bronhi
435
Adenocarcinoma
Peripheral, lobulated mass
436
Metastatic disease
Multiple random nodules
437
Lymphangicitic spread
438
P resistive
Flow x resistance
Pressure to overcome resistive forces is greater in obstructive diseases and faster breathing (higher flow)
439
P elastic
Volume x elastance
Pressure to overcome elastic forces higher in larger tidal volumes and stiffer lungs (restrictive disease)
440
Minimize work in Obstructive disease
Resistive work increased
Slow deep breaths (avoid increased flow)
441
Minimize work in restrictive diseases
Compliance is low ie elastic work is increased
Breath with lower tidal volume
442
Mechanisms of pleural fluid formation
1. Increased capillary hydrostatic pressure
2. Reduction in intravascular oncotic pressure
3. Increased capillary permeability/vascular disruption
4. Decreased lymphatic drainage or complete blockage
5. Increased peritoneal fluid, with migration across diaphragm via lymph or structural defect
443
Symptoms/physical findings of pleural effusion
Dyspnea
Chest pain
Cough
Decreased expansion
Dullness to percussion
Decreased breath sounds
Decreased tactile fremitus
Tracheal shift away from large effusion
Pleural friction rub
444
Purulent pleural fluid = ?
Empyema
445
Putrid odor pleural fluid = ?
Anaerobic empyema
446
Milky, opalescent pleural fluid = ?
Chylothorax
447
Most common causes of transudate effusions and definition
Ultrafiltrates of plasma
CHF
Hypoalbuminemia
Nephrotic syndrome
Cirrhosis
448
Exudate content and overall causes
Fluid with elevated protein content
Arise from:
Pleural/lung inflammation
Impaired lymphatic drainage of pleural space
Increased capillary wall permeability/
Vascular disruption
449
Most common causes of exudates
Parapneumonic causes
Malignancy
Collagen vascular disease
TB
PE
450
Exudate diagnosis ratios
Plural fluid protein:Serum protein \> .5
Pleural LDH:Serum LDH \>.6
Pleural fluid LDH \> 2/3 upper limit of normal serum value
451
Light criteria for exudates
PLeural fluid LDH \> .45 upper limit of normal
Pleural fluid cholesterol level \> 45,g/dL
Pleural fluid protein level greater than 2.9
452
Respiratory distress syndrome definition
Clinical syndrome characterized by respiratoyr dysfunction in infants
Deficiency of pulmonary surfactant
453
Respiratory distress syndrome pathology
Atelectasis and hyaline membranes in lung
454
RDS complications
PDA
Interventricular hemorrhage of brain (due to hypoxia)
Necrotizing enterocolitis
Oxygen toxicity to lungs
Bronchopulmonary dysplasia
455
Bronchopulmonary dysplasia
Chronic neonatal lung disease comlicating unresolved RDS --\> persistant respiratory distress
New BPD caused by disrupted lung development and alveolar hypoplasia
456
BPD pathology
Persistant lung immaturity
Chronic atelectasis
Alveolar hypoplasia
Interstitial fibrosis
457
Bronchogenic cysts
Pinched off remnant of primitive esophagobronchial tissue that form benign cyst in lung, mediastinum, or next to gut
458
Sequestrations
Portions of lung without bronchial connection with systemic arterial blood supply
Intralobar sequestrations are in visceral pleura
Extralobar sequestrations are invested by own pleura, separate from lungs
459
Pulmonary hypoplasia definition + causes
Undevelopment of lung, lacks acinar development
Extrenal compression (rib cage anomalies or diaphragmatic hernia)
Renal agenesis or disease (Potters)
Oligohydraminoas
Anencephaly
Idiopathic
Association with complex malformation syndromes
460
Bronchiectasis definition
Fixed dilation of large airways, usualy due to a previous necrotizing inflammatory process in airways --\> permanent airway scarring
461
Causes of bronchiectasis
Bronchial obstruction: Airway distended with secreted mucus, infection
Congenital or hereditary conditions
Immunodeficiency --\> repeated infections
Ciliary abnormalities
Necrotizing bronchopneumonia
462
Gross pathology of bronchiectasis
Dilated airways
Thin walls
463
Microscopic pathology of bronchiectasis
Airway dilatation
Absence of normal bronchial wall structures (glands, muscle, cartilage)
Fibrosis and chronic inflammation of airways
464
Clinical course of bronchiectasis
Chronic productive cough
Occasional hemoptysis
Episodes of acute infection
Eventually cor pulmonale and cyanosis
465
Septum transversum
Grows from ventral body wall and separates heart and liver
Connects with esophagus/foregut
Develops into central tendon of diaphragm
466
Stages of lung development
Embryonic
Pseudoglandular
Canalicular
Terminal sac stage
Post natal stage
467
Embryonic stage
4-7 weeks
Primitive airways develop and lungs begin to fill pleural cavity
468
Psudoglandular stage
8-16 weeks
Continuation of airway development - conducting airways
Lung arteries begin to form
469
Canalicular stage
17-26 weeks
Formation of respiratory bronchioles
Cells in airways become ciliated cuboidal
Intense growth of blood vessels and formation of capillaries
470
Terminal sac stage
26 weeks - birth
Alveoli form as buds
Type I and type II epithelium form
Surfactant is produced
471
Postnatal stage
Birth-5 years
Significant increase in alveoli
472
