Pulm 1 Flashcards
What is the function of the respiratory system?
Gas exchange (warm/humidify the air and filter and protect us from it)
Acid-base
Phonation
Metabolism of endogenous substances
How much blood passes through lungs each minute?
Entire blood volume (~5L)
How is the lung anatomically divided?
What are the functions of the airways (conducting zone)?
Serve as conduits of air
Provide for evacuation of foreign material
Provide immunologic and protective functions
Serve to warm and humidify the air as it enters
What are features of Respiratory Epithelium?
How do bronchi and bronchioles differ histologically?
What is the funcitonal subunit of hte lung?
Acinus
What are features that allow for efficient and rapid gas exchagne?
Large surface area
Short diffusion path
Concentration gradient
What does the lung look like at the alveolus?
What are Type 1 vs Type 2 pneumocytes?
Type 1 = cover ~95% of alveolus, but are only 40% of cells - cant’ divide
Type 2 - cover ~5% but account for 60% of cells. Divide to replace type I cells
What factors can influence anomalous funciton of thel ugns?
Gas exchange impairment in alveolar space
Increase in air flow resistance in bronchioles
Altered pulmonary mechnaics
What is ventilation-perfusion mismatch?
Area receiving blood isn’t the same as area receiving fresh air
E.g. neoplasm, mucous plugging, COPD, edema, pneumonia
What do we see here?
Mucus plugging in chornic bronchitis limits airflow to alveolar gas exchagne areas
What are alveoolar filling processes?
Pneumonia, edema
Fluid and inflammation occupies alveolar space preventing acess to the area of gas exchange
What do we see here?
Acute pneumonai - neutrophils fll alveolar spaces
How can you impair diffusing capacity?
Loss of alveolar or endothelial area (emphysema)
Thickening of alveolar wall (fibrosis)
What are two factors upon which diffusing capacity depends?
Alveolar and endothelial surface areas
Thickness of air-blood barrier
What do we see here?
Real bad emphysema - decreased alveolar surface
What do we see here?
Interstitial fibrosis - increased thickness of alveolar walls inhibits gas exchage
What are some obstacles to perfusion?
Destruciton of alveolar capillaries
Alteration of pulmonary blood flow (cardiac, pulmonary HTN)
Obstruciton of blood flow (PE, compression)
What are general features of the pulmonary vasculature?
Dual circulation:
Pulmonary arteries (low pressure, capacitance, gas exchagne)
Bronchial arteries (systemic pressure, nutrient vessels)
What do we see here?
Pulmonary HTN - increased htickenss of pulmonary vessels - decreased blood flow to gas exchange areas
What are structural mechanisms for defense in the lungs?
Nasal hairs
branching airways
Muco-ciliary escalator
Alveolar macrophages
A 55 year old man presented to the ED with shortness of breath. His exam shoes dullness to percussion, absence of breath sounds at the left base. The AP chest radiograph shows
opacification onf the left hemithorax. Fluid in the chest is suspected The next step is to order:
A. Lateral decubitus film
B. Apical lordotic film
C. CT scan of the chest
D. PA and lateral film
E. Supine chest xray
Lateral decubitus film
What is the PA view?
Patient is upright and in full inspiration
XR tube is 6 feet from film
What is the lateral CXR?
Left side of patient against XR cassette
Helpful in visualizing lesions behind the heart the mediastinum or diaphragm
What is the AP view?
Portable XR unit on sick patients - supine or sitting in bed
XR passes from anterior to posterior
Less powerful, higher magnification, less sharp images (taken from shorter distance)
Which is PA, which is AP?
What is a lateral decubitus view?
Patient lies on his side in lateral position
Helps visualize free fluid in pleural cavity as it will gravitate and layers against dependent thoracic wall
What are expiratory views?
Help visualize free air in pleural cavity (pneumothorax) as the lung markings becoem more crowded which help delineate edge of lung
What is the apical lordotic view?
Frontal view taken with XR beam angled to project clavicles above the lung apex to display disease hidden behind the clavicles
Seen on right
Identify the structures on this xray
Identify the structures
What are demarcations of the right and left lung?
Right has RUL, RML, RLL
Left has LUL and LLL
Major fissure separates RUL and RML from RLL on right and the LUL from LLL on left
Minor fissure separates RUL from RML
what is lung compliance?
Volume/Pressure
What is the compliance of the chest wall?
What is the compliance of the respiratory system?
Combination of the chest wall and lungs
What is hysteresis?
The chest wall compliance is different in inflation than in deflation
Why is there hysteresis?
Surface tension increases the pressure needed to expand the lung
Surfactant helps
What are surface forces of the lung?
Air liquid interface adds to pressure to required to expand lungs
Saline filled lungs requrie less pressure
Surfactant reduces surface tension (decreases further when lungs get smaller) and prevents small airway and alveoli collapse
Surfactant is made by Type II pneumocytes
What cells make surfactatn?
Type II pneumocytes
What are tissue forces of elastic recoil/
Beyond a certain point of inflation, lungs get stiff
Below a minimum, alveoli stay open because of their structur
How does compliance change with disease?
ΔV/ΔP
What decreases lung compliance?
Pulmonary fibrosis
Pulmonary Edema
Pneumonia
What increases pulmonary compliance?
Epmhysema
Normal Aging
What do you see here?
Left: normal
Right: empnysematous lung - decreased elastic recoil, increased airflow resistance
What are pressures during tidal breath?
Pleural- always negative
Alveolar - correlates with flow
What is Reynolds number?
Density * diameter * velocity / Gas viscocity
Higher number => turbulent flow more likely
What characterizes air flow in large airways?
Turbulent flow
Resistance increases as flow increases
Helium/oxygen mixture decreases density and increases viscocity and is used to improve flow during turbulent flow conditions (upper airway obstuction)
How can you improve flow under turbulent flow conditions (e.g. upper airway obstruction)?
Provide a helium:oxygen mixture that decreases density and slightly increases viscocity improving the Reynolds number
What descries airflow in smaller airways?
Laminar flow and Poisseuille’s Law
Resistance is proportional to viscocity*length/radius^4
Airway radius is most impmortant factor in resistance
Where is there the most resistnace to airflow?
Larger airways - there are SO many smaller airways, that the laminar flow dynamics of the small radii doesn’t come into play
What does FEV1/FVC ratio decrease indicate?
Obstructive defect
What defines restriction?
Reduced lung volumes (not just spirometry)
What does reduced “diffusion capacity” indicate?
Gas transport defect, but not much else
What are spirometry measurements?
What are the lung volumes?
What should your FEV1 typically be?
~ 3/4 of full expiratory volume (vital capacity)
How do you measure FRC, and by extension reserve volume?
Helium dilution after equilibration
Body phlethysmography
Does diffusion limit oxygen transport?
No - a RBC spends more than enough time in the capillary to diffuse (1 second or so)
In a patient with emphysema, lung compliance would be expected to be
A) Decreased
B) Increased
C) Generally unchanged
D) Cannot predict
Increased - not necessarily a good thing
Most of the resistance to airflow in the lung comes from
A) Large airways B) Small airways C) Alveoli
Large (not intuitive)
Functional Residual Capacity is the volume of the lungs
A) When you take the biggest possible breath B) When you let all your air out
C) When you are dead
When you’re dead
What is physiologic dead space?
Total volume of lungs that doesn’t participate in gas excahnge
Anatomic dead space (conducting airways) + functional dead space (ventilated alveoli that do not participate in gas exchange)
What is the anatomic dead space?
Volume of conduncting airways (~150 mL)
Nose, mouth, trachea, bronchi, terminal bronchioles
What is functional dead space?
Abnormal to have
Ventilated alveoli that don’t participate in gas exchange
Due to mismatch of ventilation and perfusion (v and q)
How do we measure dead space?
compare partial pressure of CO2 in alveoli and partial pressure of CO2 in expired air
VD = VT X [(PaCO2 – PECO2)]/ PaCO2
You typically use Vd/Vt ratio: Vd/Vt = (PaCO2 - PeCO2) / PaCO2
What is minute ventilation?
Tidal volume * respiratory Rate
Ve = Vt * RR
what is normal tidal volume?
450-500mL
What is normal minute ventilation?
~6.3 liters/minute
What is alveolar ventilation?
Minute ventilation - dead space ventilation
Va = RR*(Vt - Vd)
What is the alveolar ventilation equation?
INverse relationship between alveolar ventilation and alveolar PACO2 when the rate of CO2 produciton is constant
PACO2 = VCO2 * K / VA
K = constant for body temp, ampbient pressure standard (863)
What does the alveolar ventilation equation tell us?
If VCO2 doubles (strenuous exercise) then the only way to maintain the normal value of PACO2 is for VA to double also
When VA is doubled then PACO2 is halved
What is the alveolar gas equation/
Describes relationship between alveolar CO2 and O2
PAO2 = PIO2 - PACO2/R
R is respiratory exchange ratio (CO2 produciton/O2 consumption); normal is 0.8
What ist he normal respiratory exchange ratio?
0.8
A man has a rate of CO2 production that is 80% of rate of O2 consumption. If his arterial PCO2 = 40 mmHg and PO2 in humidified tracheal air is 150 mmHg, what is his alveolar
PO2?
Assume arterial blood equilibrates with alveolar. So PaCO2 = PACO2
PAO2 = PIO2 - PACO2/R
150-40/.8 = 100mmHg
How is perfusion different in the lung?
Zone 1= apex
Zone 2 = middle
Zone 3 = base - best perfusion
How is ventilation different in different regions in the lung?
Also varies with gravity
Gravity produces differences in regional ventilation
V is highest in base of the lung
How is V/Q different throughout the lung?
Actually ends up being highest at the top of the lung!
Which area of the lung has best V/Q ratio, which has lowest?
Highest in zone 1 (top)
Lowest in zone 3 (base)
What is happening when V/Q = 0?
Shunt = perfusion without ventilation
What happens when V/Q => infinity?
Ventilation without perfusion
dead space
What is Dead space (V/Q = infinity)?
Since there is lack of blood flow, O2 can’t be received or CO2 cant be added to alveolar gas
E.g. Pulmonary Embolism
What occurs in a shunt?
Lack of ventilation
NO O2 from alveolar gas to deliver to blood ro CO2 from blood to be eliminated
E.g. airway obstruction or right to left cardiac shunt (ASD)
What is the fractional concentration of oxygen in the air?
21 % so partial pressure is 760 *.21= 160 mmHg
How does the partial pressure of oxygen change from atmosphere to lungs?
Humidified air includes vapor pressure of weather
Atmosphere is 21% oxygen so 760*.21, but humidified is 760 - vapor pressure of water
so its less
What is venous partial pressure of oxygen?
40
What is venous partial pressure of carbon dioxide?
46
What is arterial partial pressure of oxygen?
100
What is arterial partial pressure of carbon dioxide?
40
What is perfusion limited gas exchange/
Total amount of gas transported across alveolar/capillary barrier is limited by blood flow (perfusion)
Partial pressure gradient isn’t maintained, so only way to increase amoutn of gas transported is by icnreasing blood flow
How do O2, CO2, and N2O Gas exchange?
Perfusion limited
What is diffusion limited gas exchange?
Total amount of gas transported across the alveolar-capillary barrier is limited by diffusion process
As long as partial gradinet is maintained, diffusion will continue along the lenght of capillary
e.g. CO
How does CO gas exchange?
Diffusion limited
What are examples of diffusion limited gas exchange?
CO
O2 in emphysema, pulmonary fibrosis or exercise
How much oxygen/gm does hemoglobin carry?
1.34
What is the O2 content of blood?
O2 bound to HbA + Dissolved O2
Bound to HbA is Hb conc * 1.34 * % saturation
WhatisO2 contentofthe blood of a patient with anemia (Hb 10 gm/dL)?
Assuming normal lungs hence normal PAO2 of 100 mmHg and normal PaO2 of 100 mmHg
Hb is 98% saturated at PaO2 of 100 mmHg
O2 boundtoHb=10gm/dLx 1.34 mL O2 / gm Hb X 98% (saturation) = 13.1 mL O2/100 mL blood
Total O2 content = above value + dissolved O2
Dissolved O2 = PaO2 X solu = 100 mmHg X 0.003 mL O2/100 mL/mmHg = 0.3 mL O2/100 mL blood
Total O2 content = sum of above = 13.1 + 0.3 = 13.4 mL O2/100 mL blood
What is the O2-Hb Dissociation curve?
Reversible binding of up to 4 molecules of O2
P50 = PO2 at which Hb is 50% saturated = 24 mmHg
What makes the O2-Hb dissociation curve shift to the right?
<!–anki–>
Decreased affinity of Hb for O2
Increase in P50
O2 unloading is facilitated
Due to acidic pH or higher PCO2: BOHR effect (exercising skeletal muscles)
Due to higher temp (exercise)
Higher 2,3-DPG conc: byproduct of glycolysis in RBC, under hypoxic conditions, binds Hb & reduces affinity for O2
What makes the O2-Hb dissociation curve shift to the left
Increased affinity of Hb for O2
Decrease in P50
Decreased unloading of O2 to tissues
Decrease in PCO2 & increase in pH
Decrease in temp
Decrease in 2,3-DPG conc
HbF: βchain replaced by γ chain and 2,3-DPG doesn’t bind as avidly to γchain
What occurs when carbon monoxied is in the blood?
Affinity for Hb is 250x that of O2
Presence of CO decreases available heme units, but ALSO shifts the curve to the left
Combined effects are catastrophic to tissues
How is CO2 transport in the blood carried out?
What is hypoxemia?
Decrease in arterial PaO2 (decreased oxygen in blood)
What is the A-a gradient?
Difference between alveolar and arterial O2 (PAO2 - PaO2)
How do we get measurements of PaO2?
blood gas machine
How do we get measurements of PAO2?
Alveolar gas equation
PAO2 = PIO2 - PaCO2/R
What is a normal A-a gradient?
< 12 mmHg
What are causes of hypoxemia?
High altitude
Hypoventilation
Diffusion defect
V/Q defect
R->L shunt
What is the effect of high altitude?
Low barometric pressure -> decreases PO2 of inspired and alveolar air
Diffusion is normal, and capillaries are normal, so PaO2 = PAO2 , so no A-a gradient defect
Supplemental O2 helps
What is the effect of hypoventilation?
Decreased alveolar PAO2
O2 equilibration is otherwise normal so A-a gradient is normal
Supplemental O2 increases alveolr PAO2 and helps
What are the effects of diffusion defects?
E.g. pulnoary fibrosis or pulmonary edema
Increases idffusion distance or decreases available surface area
O2 equilibration is impaired, so A-a gradient is increased
Supplemental O2 helps by increasing PAO2 and increasing driving force of diffusion
What are the effects of V/Q defects?
Increased dead space or high V/Q = clot in pulmonary artery
Increase shunt or low V/Q = area of alveolar flooding (pus in pneumonia or obstruction of airway)
A-a gradient is increased
Supplemental O2 can help by raising PO2 of low V/Q units where blood flow is highest
(Supplemental O2 can help, but may not in some cases)
What is the effect of a right-to left shunt?
Blood compeletely bypasses alveoli
Deoxygenated blood mixed with normally oxygenated non-shunted blood and dilutes it
A-a gradient is increased
Supplemental O2 doesn’t help because shunted blood keeps diluting normally oxygenated blood
What is Hypoxia?
Decreased oxygen delivery to tissues
O2 delivery has two coponents: Cardiac output * O2 content of blood
O2 content: biggest contributor is Oxy-Hb
What are causes of hypoxia?
Hypoxemia
Decreased cardiac output
Anemia
CO poisoning
CN poisoning
What is normal blood pH?
7.38 - 7.42
What is normal PaCO2?
40 mmHg
What is normal PaO2?
100 mmHg
What is the relationship between hydrogen ions (H+) and PCO2 and HCO3?
Directly proportional to CO2, indirectly to HCO3
H+ = 24 * PCO2/[HCO3]
How does hte body compensate acid-base disturbances acutely? chronically?
Pulmonary = acute (minutes)
Renal = Chronic (hours/days)
What are the primary acid-base disturbances?
Respiratory acidosis or alkalosis (PaCO2 too high or low respectivley)
Metabolic acidosis or alkalosis ([HCO3] too low or high respectively)
How do you approach acid-base analysis?
1) pH acidemic (<7.35) or alkalemia (>7.45)
2) Is primary metabolic or respiratory -> look at PCO2
3) If respiratory: acute or chronic: Acute: larger change in pH (0.8*(PCO2-40)/10) vs chronic: 0.3 *..)
4) If metabolic, compensated: Winter’s formula
5) If metabolic, anion gap?: Na - (Cl + HCO3) = anion gap elevated if > 12
What are soem causes of respiratory acidosis?
Chronic resp diseases: COPD, emphysema
Drugs: opiates, alcohol, hypnotics, anesthetics
Neuromuscular disease: Guillain-Barre, muscular dystrophy, myasthenia gravis
Obesity-hypoventialiton syndrome
What are potential causes of metabolic alkalosis?
H+ losses via GI or renal tract (vomiting or urine)
Intracellular movement of H+
Increased bicarb reabsorption by kidnesy (due to decrease in effective circulating volume (contraction alkalosis))
Exogenous alkali administration
Sustained elevated bicarb due to: volume depletion, chloride depletion, hypokalemia
What typically causes an elevated ion gap?
Rise in unmeasured anions:
MUDPILES
Methanol
Uremia
Diabetic Ketoacidosis
Paraldehyde or Metformin
Iron tablets or INH
Lactic acidosis
Ethylene glycol
Salicylates
What causes non-anion gap acidosis?
Loss of bicarb (diarrhea, or Gi tract)
Decreased H+ excretion in kidnesy (renal failure)
What is the compensation formula for metabolic acidosis?
PaCO2 = 1.5 * [HCO3] + 8 +/- 2
What is the compensation formula for metabolic alkalosis?
PaCO2 = 40 + [0.7*([HCO3]-24)]
What makes up the respiratory center?
Dorsal respiratory group (primarily responsible for inspiration, gets input from vagus and glossopharyngeal)
Ventral respiratory group (for inspiration and expiration, not as important)
What are inputs of ventilatory drive?
Chemoreceptors: medulla, carotid body, arotic arch
Lung receptors (stretch, J receptors, irritant receptors, chest wall)
What are central chemoreceptors?
Near surface of medulla (not same as medullary respiratory centers)
Responds to CO2 (pH)
On “brain side” of BBB
CO2 diffuses across quickly, charged particles (H+) do not
Very fast responses to small changes in PCO2
What are peripheral chemoreceptors?
Carotid bodies and aortic bodies
Thoguth to mostly respond to oxygen and some respond to CO2, especially in hypoxemia
Also respond to changes in arterial pressure
What is the hypercapnic drive?
~ 2 L/min/torr
Normal response to PCO2 of ~ 43 mmHg woudl be to more than double your minute ventilation
Elevated PCO2 is abnormal - you respond quickly and robustly
What is the hypoxic drive?
Mediated by peripheral chemoreceptors
Magnitude of response is smaller than hypercapnic drive
Not uncommon to be hypoxic with little to no dyspnea though
What are the role of lung receptors in breathing contorl?
Can give you normal blood gases with shortness of breath
“can’t do” or “won’t do”
What are stages of non-REM sleep?
Stage 1 : light sleep, easily arousable
Stage 2 : about 50% of sleep time
Stage 3 : “slow wave” or “delta” sleep -> deepest, most refreshing, most in children
What is the effect of sleep on ventilatory dirve?
Reduces
PCO2 rises about 2-6 mmHg on transition to sleep, and is associated with some respiratory irrregularity
Slow wave sleep (stage 3) - very regular breathing - body on autopilot
REM sleep - further decrease inv entilatory drive, greater dependence on diaphragm, decreased muscle tone
What is obstructive sleep apnea??
Common - more common in overwieght, family history
Major risk factor for MI, stroke, CHF
What is central sleep apnea??
Ventilatory drive problem
Seen in some obese patients (rare)
“Ondine’s curse” - rare in reality, common in textbooks - defect in PHOX2b gene - congenital central hypoventilation syndrome
How does Obstructive Sleep apnea occur?
Upper airway msucles normally contract ot actively keep airway patent
Sleep decreases muscular activity (especially REM)
Increased occurence with supine posture, obesity, or crowded airway
How do you asses the severity of obstructive sleep apnea?
Number of sleep related obstructive breathign events
Mild = 5-15 per hour of sleep
Moderate = 15-30
Severe > 30
What is cheyne-stokes respiration/
Periodic breathign with central apneas
Best example is CHF with increased circulation time (delayed thermostat)
What is exercise?
Increased oxygen consumption
Must increase cardiac output and increase minute ventilation
Can increase minute ventilation ~ 20x
ABGs are unchanged
What occurs to muscle oxygen extraction during exercise?
Increases from ~ 20% of cardiac output, to about 80% at maximal exercise
How do arterial blood gases change during exercise?
PaO2 same
PaCO2 same
pH declines during strenuous exercise
CO2 produciton increases from lactate metabolism (anaerobic threshold)
What typically limits exercise capacity?
Cardiac output (stroke volume) in most people
What is cough?
Non-specific symptom of respiratory disease, with broad DDx
Most common symptom world-wide for which patients seek medical attention
Protective physiologic reflex; defense mechanism for protecting airway and clearing foregin particles
Can spread disease and can represent serious medical disease or benign disease
Can be non-voluntary or voluntary
What are features of an effective cough?
Depends on capacity of respiratory muscles: increase intrathoracic pressures, dynamic compression of airways
Drives gas at high linear velocities (up to 100 mph)
Depends on effective interaction between flowing gas and mucus lining in the airways (loosens mucus, removes it from airways; works in concert with mucociliary escalator, abnormal mucus makes it difficult)
What are the three phases of coughs?
1) inspiratory: inspire any amount of air. larger => optimizes lenght-tension relationship
2) compressive: glottis is closed and expiratory effort ensuse - maintain lung volume and build pressure
3) expiratory: high expiratory flow rate and blast of turbulent flow ensues
What is the cough reflex?
Cough begins with stimulation of receptors in and under airway epithelium
Must abundant in larynx and large airways
Stimulated by irritants or inflammatory mediators by activating GPCRs (bradykinin B2, prostanoid EP3 receptors)
Two types of sensory afferents mediate it:
Aδ fibers: originate from nodose ganglia and are sensitive to mechanical stimuli
C-fibers: originate in jugular vagal ganglia and are chemosensitive (noxious chemicals)
Activation of these to vagus, synapse in solitary tract nucleus in medulla, to cough center via second order neurons
What are the afferents that mediate cough?
Aδ: originate in nodose ganglia, sensitive to mechanical stimuli
C-fibers: originate in jugular vagal ganglia and are chemosensitive (bradykinin and capsacin)
These then go to vagus, synapse in solitary tract in medulla to cough center via second order neurons
What are TPR channels?
Transient Receptor Potentail - superfamily of ion channels expressed in sensory neurons
TPRA and TPRV have been implicated in cough; open and activate afferent nerves and respond to noxious stimuli
In disease, these receptors can become sensitized and hyperresopnsive
What are the efferent components of the cough reflex?
Activated to produce cough:
Vagus- supplies larynx and tracheobronchial tree
Phrenic - supplies diaphragm
Spinal motor nerves - supply expiratory muscles
Why do we cough?
Excessive stimulation of cough receptors - too much mucus, foreign body
Stimulation of afferent vagus (rare) - mediastinal tumor, aortic aneurysm
Heightened sensitivity to cough receptors - ACE inhibitors, airway inflammation
What is the role of ACE inhibitors in cough?
Common side effect - proposed mechanism:
ACE also metabolizes bradykinina dn substance P - these molecules accumulate and produce cough
What are causes of acute cough?
Viral URT infection
Exacerbation of underyling lugn disorder
Acute environemntal exposure
Acute cardiopulmonary disease
What are subactue coughs?
Postinfectious cough
Non-postinfectuous
What are causes of chronic cough?
Active cigarette smoking or chronic irritant
ACE inhibitor use
Radiographically apparent disease process in lung
Other: upper airway cough syndrome, asthma, nonasthmatic eosinophilic bronchitis, GERD
What can cause impairment of cough?
Neuromuscular weakness (expiratory weakness, chest wall disorders, inspiratory weakness)
Vocal cord paralysis
Abnormal properteis of mucous (COPD, Cystic fibrosis)
What are complicaitons of cough?
Many many
Constitutional
Respiratory
CV
GI
GU
MSK
Neuro
Skin
25 y/o man presents with 24 hour history of non-productive cough. denies other symptoms. started after he chocked on chicken bone that he thoguht he swallowed. cough is initated by:
A- efferent neurons that supply larynx and trachea
B- Αδ fibers from nodose ganglia
C- medullary cough center
D- adrenergic nerve innervation of airways
E- inflammatory mediators bradykinin and prostaglandins
B - Aδ fibers from nodose ganglia - mechanical!
What is dyspnea?
Breathing discomfort; distressed feeling associated with breathing
What is tachypnea?
Increased respiratory rate - response to increased CO2 production, or CO2 elimination that exceeds CO2 production
What is apnea/hypopnea?
Absence of or inadequate ventilation (central or obstructive sleep apnea)
Where does the sensation of dyspnea arise from?
Periphearl receptors throughotu respiratory system
Sense of effort from cortex when efferent messages are transmitted to respiratory muscles
Psychological, social, and environmental factors
How is the intesnity of dyspnea modified by?
Relationship between expected airflow and displacement of lugns and chest wall for given motor command and the ACTUAL acheived output of the ventilatory pump
What can cause neuro-mechanical dissociation of expected and actual airflow?
Excess ventilatory drive
Decreased ability to perform work of breathing
Excessive work of breathing
What mediates dyspnea?
Mechanoreceptors (stretch, J, and irritant receptors)
Chemoreceptors (medullary, carotid, aortic bodies)
Sensation of respiratory effort in skeletal muscles of chest wall, etc)
How can you objectively assess dyspnea?
Use of accessory respiratory muscles, tachypnea, cyanosis, hyperinflation
What can cause dyspnea?
Increased ventilatory drive -> anxiety, pain, fever, sepsis, increased dead space, increassed CO2 production, metabolic acidosis, hypoxia, medications
Increased work of breathing-> chest wall deformity, pleural effusion, pneumothorax, pulmonary fiborsis/interstitial lung disease, pulmonary edema, pnemonia, lower and upper airway disease
What is hemoptysis?
Coughing up blood from airways or lungs - from mild bronchitis to fatal cancer
have to exclude epistaxis, oral, esophageal or gastric sources
DDx is broad
What are major sources of hemoptysis?
Pulmonary, bronchial, alveolar-cappillary interface, mucosal or peribronchial plexus, endobronchial lesions
What is pleuritic chest pain?
Chest pain worsening with inspiration or movement
Originates form parietal pluera, which has pain fiber innervation (visceral pleura and lung parenchyma dont
Can be inflammatory or traumatic, well localized
What are pulmonary causes of chest pain?
Infection (lung or primary pleura)
Inflammation
Infarction
Pneumothroax
Tumor (met, primary pleura, or lung tumor)
what are non-pulmonary/cardiac causes of cehst pain?
MSK
Psychogenic
GI (GERD, motility disorders, splenic flexure syndrome, pancreatitis)
What are mechanisms of lung defense
Mechanical barriers
Mucociliary transport
Cough and othe rreflexes
Innate immune system (secretory molecules, cellular components)
Adaptive immune system (antibodies)
What is the funciton of the nose?
Air is warmed to within 1 degree of body temp
Almost completely humidified
Partially filtered
How does the nose act as a filter?
Hairs at entrance filter out large particles
Air hits many obstructing structures (turbinates, septum, pharyngeal wall)
Particles cant change direction as rapidly as air and striek surfaces adn are entrapped by mucous and transported by cilia to be swallowed
What is the most important determinant of how a foreing particle will interact with respiratory system?
Size
How does the mucociliary transport work?
Cilia beat in a coordinated fashion
Mucous velocity can move at up to 25 mm/min
HIghly efficient mechanism that can clear mucous blanket of entire nose or sinus in 10 minutes
How are cilia typically arranged on the microtubule level?
Circular
What happens when protective mechanisms are overwhelmed?
Accumulations of mucus - can be large and block airways; can also become infected
What is mucus?
90% water, 10% of protein, carbohydrates and lipid
Non-aqeuous constituents - sol or gel phase, or both, depending on solubility
Proteinc onstituents: mucin glycoproteins, proteoglycans, variety of proteins (MUC genes - glycoproteins)
What are funcitons of mucus?
PReserves membrane (lubricates, humidifies, waterproofs, insulates, provides environment for ciliary action)
Acts as barrier (entraps microorganisms, particulates, provides sruface for Ig action, neutrolyzes toxic gases)
Transports trapped materials
What is mucociliary clearance?
Defense mechanism of ciliated epithelial cells that propels airway secretions towards mouth
Normally: periceliary liquid layer (PCL) is the layer of fluid that bathes cilia - located between apical membrane of epithelial cells and base of overlying mucus must be of optimal depth
Water movement into and out of PCL is mediated by active ion tranpsort (where Cystic fibrosis comes into play)
What is teh source of mucin
GOblet cells
Submucosal galnd cells
Intracellular granules
Submucosal gland cells are cholinergically innervated (unlike goblet cells); release mucus when innervated
What is the sneeze reflex?
Very much like cough reflex, except applies to nasal passageways
Initiating stimulus is irritation of nasal passageways
Afferent impulses pass in CNV in medulla
Series of reactions similar to those for cough take place, however the uvula is depressed so large amounts of air pass through the nose, helping clear it of foreign matter
What are secretory molecules of innate defenses of the lungs/airway?
Complement - lysis and opsonizaiton of bacteria
Lactoferrin/transferrin - bind iron and limit bacterial growth
Interferons - limit viral replicaiton
AMPs = antimicrobrial peptides (β-defensins, cathelicidins) - kill bacteria
NO - toxic ot microorganisms
Lysozyme - breakds down bacterial walls
Proteolytic enzymes and cathepsinG - break down proteins
Surfactant proteins (SP-D) bind ot microorganims
What are the sentinel cells of the lower airway?
Pulmonary dendritic cells (just under epithelium with pseudopods inot airway - capture particles
Pulmonary macrophages reside in lumen and capture and engulf particles
What is normal bronchoalveolar lavage fluid?
< 95% alvoelar macrophages
< 4% lymphocytes
< 2% granulocytes
< 2% monocytes
< 0.4% dendritic cells
What molecules differentiate pathogen from non-pathogen in order to activate the immune system only when necessary?
TLRs
A 19 year old man presented to the ED with pneumonia. Since age 6 months he has had recurrent pneumonia and sinusitis due to Streptococcus pneumoniae and Haemophilus influenzae. His immune status would likely reveal abnormal function of:
- A. B Lymphocytes
- B. macrophages
- C. natural killer cells
- D. platelets
- E. T Lymphocytes
A - B lymphocytes
A 68 year old miner has been inhaling coal dust for 45 years. His immune system has cleared the dust particles that he has inhaled. Which of the following cells is most abundant in the alveoli to begin this innate immune process?
A. Alveolar Macrophages
B. Lymphocytes
C. Granulocytes
D. Monocytes
E. Dendritic Cells
A - Alveolar macrohpages
What is asthma?
Chronic inflammatory disease characteraized by recurrent episodes of wheezing, breathlessness, chest tightness and cough
Associated with widspread but variable ariflow obstruction that is partially reversible either spontaneously or as result of treatment
Inflammation also causes increase in bronchial hyperresponsiveness
What are distinguishing features of asthma?
Diffuse airflow obstruction of large and small airways
Reversibility of airflow obstruction (spontaneous or result of therapy)
Bronchial hyperresponsiveness to challenge (with specific or non-specific inhalation agents)
How do you physiologically measure asthma?
Spirometry
PEFR measurements with peak flowmeter
Lung volume determinations
ABG analysis
Bronchoprovocation testing
What are the mechanics of asthma?
Poiseuille’s law - central problem is narrowed small ariways leadign to increased resistance that reduces air flow (flow proportional to radius^4)
Resistance is not constant: inhalation - low intrathoracic pressures open airways; exhalation: postivie pressures can cause airway collapse
EXPIRATORY obstruction -> like one way valves
What is airtraping?
Some lung gets over-inflatted. Some lung gets compressed (hypoxia, hypercarbia)
Overall can become overinflated -> stretched diaphragm muscles, plus high ariway resistance -> increased work
How do you mesure airway obstruction?
FEV1 (fractional expiration volume in 1 second)
What is the effect of bronchodilators on asthmatic lugn obstruction?
REVERSES obstruction
What are diagnostic criteria for asthma with respect to reversibility?
>12% improvement in FEV1 over after short-acting bronchodilator or after weeks of corticosteroid therapy or wtih spontaneous remission
20% variation in peak flow within 24 hour period (biurnal variation)
What happens to lung volumes and ABGs in asthma?
Lung hyperinflation (TLC, and FRC increased)
Air trapping (increased RV)
V/Q mismatch (Low V/Q leads to hypoxemia)
Respiratory alkylosis (hypoxemia/anxiety/reflexes)
Respiratroy acidosis - late (Severe V/Q mismatch, respiratory muscle fatigue)
What is bronchial hyperresponsiveness?
Exaggerated bronchoconstrictive response to specific (not everyone responds, e.g. allergen) or non-specific (everyone responds, eg. methacholine)
Can be quantified by bronchoprovocation tests (allergen, methacholine, histmaine challenge, cold air)
Who has greatest prevalence for asthma?
Peak is in childhood (10%) -> declines to 5-6% in adolescents -> rises to 7-9% in adults
What are risk factors for developing asthma?
Genetics and environment
Genetics: increased prevalence in 1st degree relatives, twins, association with atopy
Env: airborne allergens, viral respiratory infections, tobacco smoke, air pollution, occupation, lifestyle
What is the pathobiologic etiology of asthma?
Basal chronic inflammaiton exacerbated by acute ifnlamation that leads to structual change sover time
What occurs during the acute response of asthma?
Mediator release -> bronchoconstriction
Muscle contraction, muscle shortening, increased luminal resistance
What occurs in chronic inflammaiton in asthma?
Cellr ecruitment, epithelial damage, early structural changes
What is the relationship between allergy and astham?
Allergic astham is most common phenotype of astham
Sensitization in susceptible popoulations to indoor allergens -> housd-dust mite, animal dander, cockroaches, outdoor fungi)
Developing sensitivity to allergen can be cause of asthma (Declines with age)
Food allergens do not cause asthma
Reduce exposure to reduce asthma
What is the atopic response?
Seen in asthma (Th2 phenotype)
What is Th2 role in asthma?
Th2 response is atopic response to aeroalelrgens also toe extracellular pathogens such as helminths and certain bacteria
Th2 cells release IL-4, IL-5, IL-13, IL-9 which promote anitbody response and involves mast cells and eosinophils
What do Th2 cells do? (as a result of their cytokines)?
Allergen specific synthesis of IgE (IL-4)
Recruits eosinophils (iL-5)
Recruit and promote growth of mast cells (IL-9)
AHR and mucus production (IL-13)
What is the basis hygeine hypothesis?
Biases immune response to Th2 -> can see more asthma this way
What happened in this asthmatic?
Lumen obstructed by secretions of mucus admixed with inflammatory exudates
Severe mucous plugging in acute severe asthma
How does aireway remodeling occur in chronic asthma?
Smooth msucle mass increased
Mucous gland hypertrophy
Blood vessels engorge
Inflammatory cells persist
Collagen (Types 3 and 5) deposited in basement membrane (lamina reticularis) and in the extracellular space
What are clinical manifesttions of asthma?
History of cough (worse at night), recurrent wheeze, recurrent difficulty breathing, recurrent chest tightness)
Wheezing - high pitched whistling sounds when breathing OUT: not necessary for diagnosis
Symptoms occur or worsen at night, waking the patient
A 26 year old woman presents with shortness of breath on exertion. She was formerly able to play several sets of tenjis but lately gets shortness ofb reath after several games She has a history of allergic rhinitis and otherwise a negative past medical history. Her spirometry is normal. What test can best offer a diagnosis?
- A. Post bronchodilator spirometry
- B. Plethismography lung volumes
- C. Methacholine challenge test
- D. Serum IgE level
- E. Total eosinophil count
C - methacholine challenge test (non-specific challenge)
What is emphysema?
Abnormal permanent elnargement of air spaces distal to the terminal bronchiole, accompanied by destruciton of their walls
What is chornic bronchitis?
Presence of chronci productive cough for at least 3 consecutive months in 2 consecutive years
What is COPD?
Chornic obstructive pulmonary disease: disease characterized by airflow limitation that is not fully reversible
The ariflow limitation is progressvie and associated with abnormal inflammaotry response of the lungs to noxious particles and gases
What are causative agents of COPD? (i.e. aggressors)
Cigarettes (developed world)
Fossil fuel burning (developing world)
What is the association with smoking and COPD?
Major risk facotr
~90% of COPD patients ahve smoking history
However, only 15-20% of smokers develop COPD
What are histopathological features of COPD?
Chronic bronchitis (bronchiolitis) - thickening of airway wall and infiltration with inflammatory cells
Emphysema (destruction of alveolar walls) -. loss of attachments and airway collapse
What is the progression of COPD?
Normal -> hyperproduction of mucus -> inflammation and mucus -> end-stage
Why is airflow limited in COPD?
Destruciton of attachments of alveoli to airways, mucus hypersecretion, fibrosis and inflammation
What is the result of lung elastic recoil loss?
Airway obstruction
What is the pathophysiology of COPD?
Funcitonal abnromalities in bronchitis (airway narrowing from inflammation -> diminished flow rates adn air trapping (increased Reserve volume))
Funcitonal abnromalities in emphysema (loss of fucntioning architecture - loss of recoil, collapsibility of airways, increased lung volumes)
Hyperinflation - chronic obstruction leads to air trapping, diaphragm flattens causes disadvantage and inefficiency in mechanics of breathing; increased work; higher lung volumes -> dyspnea
What is the source of the decreased diffusing capacity of CO2 in COPD?
Loss of surface area for diffusion
What are spirometric measurements in COPD?
High FEV1, Higher FVC
How is COPD staged?
FEV1/FVC
How do you perform spirometry for COPD testing?
Administer adequate dose of short-acting bronchodilator (e.g. salbutamol)
Post-bronchodilator FEV1/FVC of < 0.7 confirms airlfow limitation that is not fully reversible
What findings do you see on CXR in COPD?
Emphysema - increased ucency, especially in upper lobes
Hyperinflation - flattened diaphragm (barrel chest)
What are three types of emphysema?
Centrilobular -> holes in centrilobular area
Panlobular -> uniform dilatation of airspaces from respiratory bronchioles to alveoli
Paraseptal -> subpleural well-defined cystic spaces -> can be bullous lung disease
What do we see ehre?
Normal lung
What do we see here?
Centrilobular emphysema
What do we see ehre?
Panlobular emphysema
What do we see here?
Paraseptal emphysema
What is the natural history of COPD?
Annual loss of FEV1 is ~ 50-100mL per year
Greater decline in patients with hypersecretion of mucus (chornic bronchitis)
Extertional dyspnea ~40% FEV1
Dyspnea at rest ~20% FEV1
Increased CO2/cor pulmonale ~ 25% FEV1
Why does COPD only present after many many years of smoking, etc? (why does it present late)?
Affects small airways -> this provides the LEAST resistance since there are so many -> requires lots of involvvement ot begin to see symptoms
What are causes of progressive airway obstruction in COPD?
- Proinflammatory mediators
- Proteolytic digestion of lung tissue
- Oxidative stress
What is the primary inflammatory cell seen in the airways in COPD? How is it different than asthma?
Neutrophils!
Asthma has eosinophils
What is the role of alveoolar macrophages in COPD?
Extremely important -> recruited, present in high numbers, survive longer, release numerous chemokines
Due to cigarette smoke, and other toxins
What is the key cell for COPD pathogenesis?
Neutrophil
Recruited and activated via chemotactic factors (LTB4, IL-8). released form macrophage and epithelial cells as ar esult of stimluation by cigarette smoke
Release proteinases that break down connective tissue and stimulate mucus secretion
Release ROS and adhesion molecules taht potentiate inflammatory response and promote further neutrophil recruitment
What ist he role of proteinases in COPD?
INvolved in alveolar wall destruction
Smokers ahve high levels of neutrophil elastase in BAL fluid; adn higher when emphysema is present
NE degrades elastin in elastic tissue
Collagen breakdown and synthesis is also a feature of emphysema
What is alpha-1 antitrypsin (AAT)?
Elastase inhibitor that protects agains proteolytic degradation of elastin
Causes early COPD in smokers
Imbalance of neutrophil elastase and AAT causes COPD
What are clinical features of α1 antitrypsin?
Early onset emphysema
Lowerlobe bulae/emphysema
Unexplained liver disease
What are risk factors for COPD?
Smoking
Environmental factors, occupational exposure
Lugn growth
Airway hyperresponsiveness
Genetics
What are clinical features of COPD?
Chronic productive cough commonly presents in 5th decade with acute chest disorder
Typically 1 pack per day smoker for > 20 years
Dyspnea on effort in 6th, or 7th decade
Mucoid sputum production in morning
Wheezing and dyspnea can lead to erroneous diagnosis of asthma
Poor quality of life and prognosis in later life
What are acute exacerbations of COPD?
Acute event characterized by worsenign of patients respiratory symptoms that is beyond day-to-day variations and leads to change in medications
What are potential causes of acute COPD exacerbations?
Bacterial or viral infection
Pollutants (NO, aprticulates, Sulfur dioxide, ozone)
Codl weather
Interruption of regular treatment
What is AECOPD?
Acute exacerbation of COPD
What are the common etiologies of AECOPD?
Infectious (non-infectious are ~ 20%)
What are the pulmonary effects of chornic inflammmation in COPD?
Dyspnea
Cough
Sputum production
Exacerbations
Ankle Edema
What are non-pulmonary (systemic) effects of the inflammation present in COPD?
Poor apetite/early satiety
Hypoxemia
Skeletal muscle dysfunction
CV increased risk of disease and death
Depression/anxiety/altered sleep
Osteoporosis
Anemia of chornic disease /GI bleed
A 70 year old heavy smoker presented to his physician with shortness of breath that started 3 years ago. On exam he has prolonged exhalation, decreased breath sounds and has a barrel chest. The likely cause of his lung condition
- A. Bronchospasm from cigarette smoke
- B. Destruction of intra-alveolar septae
- C. Deconditioning
- D. Decreased CNS drive
- E. Decreased work of breathing
B - Destruction of intra-alveolar septae
What do you see here?
Thick airways, large airways (even at periphery)
Poor tapering of airways
Mucus clogs
Mismatch of airway size and adjacent vessel size
Representative of bronchiectasis - irreversible dilatiation of bronchi caused by destruction fo bronchial wall and elastic elements
What is bronchiectasis?
Irreversible dilatation of bronchi caused by destruction of bronchial wall muscle and elastic elements
Obstructive: localized blockage and bronchiectasis occurs distal to this mechanical obstruction
Localized: used to be common, following childhood bronchopulmonary infections with measles, pertussis, or other bacteria
Generalized: secnodary to inherited impairment in host defense mechanisms, or acquired conditions that perrmit introduction of infectious organisms into airways
How does bronchiectasis develop?
Interplay between external insult, impaired immune system, genetics
Causes bronchial wall inflammation and destruction, leading to ciliary dyskinesia or altered bronchial dynamics
This results in ineffective mucus clearance, leading to chronic or recurrent infection and perpetuating the cycle
What are predisposing conditions for localized bronchiectasis?
Airway obstruction: foreign body, bronchial stricture, endobronchial mass
Non-obstructive (post infection) : bacterial, viral, mycobacterial
What are predisposing conditions for generalized bronchiectasis?
Post infectious: measles, pertussis, mycobacteria
Congenital: cystic fibrosis, primary ciliary dyskinesia
Immunodeficiency: Ig deficiency, HIV/AIDS
Immune mediated: Allergic aspergillus, collagen vascular disease
GERD/Aspiration
What are the most common pathogens seen in bronchiectasis?
H. flu
Pseudomonas aeruginosa
Moraxella catarrhalis
Staph aureus
Strep pneumo
Mycobacteria
Who gets bronchiectasis?
Older individuals
What are symptoms of bronciectasis?
Chronic cough
Dyspnea
Mucopurulent sputum production
Hemoptysis
Exacerbation of symptoms and need for antibiotic therapy several times a year for respiratory tract infection
What are pulmonary function tests like in bronchiectasis?
In early or mild disease may be normal
As disease advances -> airflow obstruction
Late -> mixed obstruction and restriction
Depends on extent of involvement
What do you typically see on x-ray in bronchiectasis?
Parallel line shadows (railroad track shadows), infiltrates, hyperexpansion (flattened diaphragm)
What are three different classifications of bronchiectasis on CT?
Cylindrical (common)
Varicose
Saccular/cystic (most severe)
What are typical CT findings in bronchiectasis?
“Tram lines” - horizontal course of bronchi and artery (red circle)
“Signet ring” sign: cross-section of dilated bronchi
“Tree bud” pattern - bronchiolar mucus impaction
How do you traet patients with bronchiectasis?
Long term oral antibiotics
Aerosolized antibiotics (tobramycin inhalation solution)
Other measures: airway clearance measures
Do you see hemoptysis in bronchiectasis?
Yes - major cause of hemoptysis
What do we see here?
Situs inversus
Inflitrates
Cystic bronchiectasis
What is primary ciliary dyskinesia?
Genetic disease in which you have defective ciliary structure and function
Chronic oto-sino-pulmonary disease; also have sterility (impaired ciliary mobility in vas deferens or fallopian tube)
Often seen with dextrocardia or with situs inversus (50% of individuals)
What are features for diagnosis of primary ciliary dyskinesia?
Chronic upper and lower aireway disease
Slope-decline of lung function (FEV1) with age, but not as rapid as in cystic fibrosis
What are the members of the sputum flora of patinets with primary ciliary dyskinesia?
H. flu/S. aureus
Smooth P. aeruginosa
Mucoid P. aeruginosa
Non-tuberculoid mycobacteria also isolated
What do you see here?
Bronchiectasis - the balls seen are CLASSIC for aspergillus (aspergilloma)
Cystic bronchiectasis complicated by an aspergilloma
What causes aspergillosis?
Aspergillus fumigatus is most common
Grows as septate dichotomous branching hyphae with actue angles and produce hundreds of spores
Can cause aspergilloma that can complicate bronchiectasis
What is cystic fibrosis??
Mutations in gene encoding for CF transmembrane conductance regulator (CFTR) - most common is ΔF508; and results in dysregulation of transmembrane transport of small molecules
Abnormalities in epithelial ion transport (dysregulated salt and water transport)
Increased sweat chloride
Changes in airway surface liquid - impaired mucociliary clearance
Causes BRONCHIECTASIS
What are common airway infections in cystic fibrosis?
S. aureus (first organism to infet young people)
H. flu (more common at younger age, uncommon in young adults)
Candida (most frequent, but considered harmless)
Aspergillus (seen in > 25% of pts)
Nontuberculous mycobacterium (MAC) - increasingly reported
What is the issue with pseudomonas infections in cystic fibrosis?
Early isolates may be normal
Later mucoid strains are antibiotic resistant and can be encouraged by chronic antibiotics
Once establisehd may be impossible to eradicate (forms biofilms) and can develop tolerance to host defenses and antibiotics
What is bronchiolitis?
INflammation in smaller conducting airways
Terminal to respiratory bronchioles
Intense repair process causes narrowing and distortion of small airways
INcomplete obliteration of lumen (constrictive bronchiolitis)
Complete obliteration (bronchiolitis obliterans)
What are potential causes of bronchiolitis?
INfection
Inhalation injury
Collagen vascular disease is associated with this (RA, etc.)
Post transplant
Idiopathic
How do patinets with bronchiolitis present clinically?
Infection: acute, with fever, cough, rhinorrhea, wheezing; viral in child respiratory syncytial virus; adults get it with adenovirus, influenza, parainfluenza, Legionella pneumophilia, Mycoplasma pneumonia
Inhalation exposures: may be delayed onset of cough adn breathlessness, subacute and progressive; NO2, Ammonia, Chlorine
Collagen vascular disease/post transplant: unexplained breathlessness, cough, or airflow obstruction; may be asymptomatic in early stages
What do you see on CTs in bronchiolitis?
May be negative since it involves the smallest division of the pulmonary system
Centrilobular peripheral nodules and tree-in-bud opacities may be seen
Obstruction of small airways can cause air trapping or hyperinflation
What do you see here?
Centrinodular nodules and tree-in-bud pattern of BRONCHIOLITIS
What are indirect signs of bronchiolitis on CT?
Mosaic perfusion of lungs
What do we see here?
Mosaic perfusion pattern in a patient with bronchiolitis
A 35 year old man is known to have cystic fibrosis since birth presents with severe shortness of breath and increased sputum expectoration. The patient’s sputum is likely to show:
- A. Resistant strains of Staphylococcus
- B. Neutrophils without organisms
- C. Mucoid strains of Pseudomonas
- D. Pseudomonas sensitive to several antipseudomonals
- E. Haemophilus organisms overtaking the petri dish
C - Mucoid Strains of Pseudomonas
What are the major effector cells in asthma pathophysiology?
Mast cells/Eosinophils
What are three types of asthma?
Extrinsic: type I hypersensitivity - atopic or occupational
Intrinsic: non-immune, due to aspirin ingestion, pneumonia, cold, stress, exercise, etc.
Status Asthmaticus: unremitting attacks due to exposure to previously sensitized antigen (can be FATAL)
How does asthma present grossly on pathology?
Overdistended lungs, small areas of atelectasis, thick mucus plugs in proximal bronchi
How does asthma present on microscopic pathology?
Mucus plugging
INflammation (eosinophils)
INcreased mucosal goblet cells and submucosal glands
Thickened basement membrane
Smooth muscle hypertrophy
Airway wall edema
What is unique about the airway mucus in asthma?
Can form a cast of the airways
INcreased inflammatory cells
Increased inflammatory mediators
Increased mucin concentration
What do we see here?
Mucus plugs
Denuded or altered respiratory epithelium
Eematous submucosa
ASTHMA
What do we see here?
Sub-epithelial fibrosis
Bronchial smooth muscle hypertrophy/hyperplasia
Inflammation
Thickened basement membrane
ASTHMA
What do we see here?
THICKENED BASEMENT MEMBRANE = ASTHMA
What is emphysema??
Permanent enlargement of airwasy distal to the terminal bronchiole
Accompanied by destruction of walls without obvious fibrosis
Elastic component of the alveolar walls are destroyed -> decreased expiratory drive and tethering of small airways
How is emphysema categorized pathologically?
Centriacinar (most)
Panacinar
Paraseptal
First two cause clinical significant airflow obstruction
Clinical severity is more important than histologic type for symptomatology
What is centriacinar emphysema?
Central or proximal parts of acini are affected, distal parts are spared
See both emphysematous and normal airspaces within same acinus and lobule
Seen more in UPPER LOBES, due to its correlation with HEAVY SMOKERS
What is panacinar emphysema?
Acini are uniformly enlarged from level of respiratory bronchiole to terminal blind alveoli
Associated with α1 ANTITRYPSIN (α1-AT) DEFICIENCY
What type of emphysema is seen more commonly in heavy smokers?
Centrilobular emphysema
What type of emphysema is seen with α1 antitrypsin deficiency?
Panacinar emphysema
What is paraseptal emphysema?
Distal portion of acinus only involved (proximal areas are normal)
Involves lung tissue underneath the pleura
More severe in upper half of lungs
Air spaces can become very large
In young adults, can result in SPONTANEOUS PNEUMOTHORAX if otherwise healthy
What is an association wtih a spontaneous pneumothorax in an otherwise healthy young adult?
Paraseptal emphysema (distal acinar emphysema)
What do we see here?
Centriacinar emphysema
What do you see here?
Centriacinar emphysema
What are the alleles for α-1 antitrypsin deficiency?
ZZ homozygous individuals have full blown disease
MM individuals are healthy
What do you suspect when a patient ahs early onset emphysema and unexplained liver disease and possible cirrhosis?
α1 Antitrypsin deficiency
What does ZZ α1 antitrypsin alleles indicate?
Disease -
ZZ = disease
ZM = reduced functional levels
MM = normal
What do we see on the left? right?
left - centriacinar emphysema
right - panacinar emphysema
When do you begin to see symptoms in emphysema?
When 1/3 /of functional capacity is lost
What are physical findings in emphysema?
Shortness of breath
Coughing
Wheezing
Weight loss
Barrel Chest
Breathing through pursed lips (pink puffer)
What are sequellae of emphysema?
Secondary pulmonary vascular hypertension
Death due to respiratory acidosis adn coma
Pneumothorax
What do we see here?
Bullous emphysema
What are causes of chronic bronchitis?
4-10x more common in smokers, chronic irritation and infetions
Tobacco interferes with ciliary action, directly damages aireway epithelium, and inhibits ability of WBCs to clear bacteria; infections maintain but do not initiate chronic bronchitis
How does chronic bronchitis appear grossly?
Boggy mucosa with excessive mucinous secretions, pus
How does chronic bronchitis appear microscopically?
Early: hypersecretion of mucus in large airways with hypertrophy of submucosal glands in tracheobroncial tree
Late: increase in goblet cells in small airways causes excessive mucus production and airway obstruciton; increased Reid index
Reid index: ratio of thickness of mucus gland layer to thickness of wall between epithelium and cartilage (normal = 0.4) increased in chronic bronchitis
What do you see here?
Chronic bronchitis
Reid INdex is close to 0.8-0.9 (80-90% of space is occupied by glands)
Enlarged mucus secreting apparatus
What do you see here?
Bronchiectasis
Dilated, tortuous, easily collapsible airways that extend to the visceral pleural surface
Copious purulent secretions within dilated bronchi
May be generalized and bilateral or localized depending on etiology
What do you see here?
Bronchiectasis
Markedly distended peripheral bronchi - can trace to pleural surface
Bronchial walls irregularly thickened
What do you see here?
Bronchiectasis
DIlated airways that extned to visceral surface
Causes airflow eddies, and copious secretions
What do you see histologically in bronchiectasis?
Chronic inflammation and ulceration of bronchial wall
Variable inflammation and fibrosis of adjacent alveoli
What histology does this represent?
Bronchiectasis
What are the small airways?
Less than 2mm internal diameter - NO cartilage
Membranous (terminal or respiratory)
Composed of epithelial cells (simple columnar, ciliated and nonciliated, as well as rare NE cells); connective tissue; and smooth muscle
When do you see small airway disease?
Primary: constrictive bronchiolitis (obliterative bronchiolitis) - rare
Secondary: bronciectasis, asthma, COPD, etc. - more common
What do you typically see in small airway disease microscopically?
Adjacent segment may have foamy macrophage accumulation and dilatation with mucostasis
What is fibrotic small airway disease (constrictive bronchiolitis/obliterative bronchiolitis)?
Subepithelial collagen deposition with airway narrowing and constriction
Thought to be abnormal wound healing response
Seen with chronic transplant rejection, as part of GVHD following BM transplant; but also with toxin exposure, infection, collagen vascular disease, drugs, etc.
What is this?
Constrictive bronchiolitis
Large amounts of connective tissue between airway and smooth muscle
Collagen and some inflammation hanging around
What do we see here?
Constrictive bronchiolitis - big scar next to pulmonary artery
What is bronchiolitis obliterans?
Not same as obliterative bronchiolitis (constrictive bronchiolitis)
In obliterans, you see luminal inflammatory exudates that forms plug of fibroblastic tissue (rare)
What ist he difference between constrictive bronchiolitis and bronchiolitis obliterans?
Obliterans - buildup is WITHIN lumen
Constrictive - buildup of fibrosis is in wall, outside of lumen and constricts from outside in
What is pneumonia?
Infection of the pulmonary parenchyma
What are different routes that infections can take to the lower respriatory tract?
Inhalation - carried in small droplet particles inhaled into lungs
Aspiration - unable to protect ariways from secretions by glottic closure and coughing
Bloodstream - less common
Why does pneumonia happen?
Defect in host defenses
Exposure to particularly virulent organism
Overwhelming inoculum
What are host defenses that fail or are overcome in pneumonias?
Branching of airways and predisposition of airways to deposition by inhaled material
Antimicrobial peptides
Phagocytic/inflammatory cells
Adaptive immune responses
What is the virulence factor of chlamydophilia neumoniae?
Ciliostatic factor
What is the virulence factor of mycoplasma pneumoniae?
Shears off cilia
What is the virulence factor of influenza virus?
Reduces tracheal mucus velocity
What is the virulence factor of streptococcus pneumoniae?
Proteases that split secretory IgA and has a capsule taht inhibits phagocytosis
What are the virulence factors of mycobacteria and legionella species?
Resistant to microbicidal activity of phagocytes
What is strept pneumoniae?
Gram positive cocus in pairs or diploccoci
50% of pneumonias requiring hospitalization
Normal inhabitant of pharynx
Polysaccharide capsule protective from phagocytosis
What is staph aureus?
Gram + cocus inc lusturs
Seen as secondary complication of influenza virus; seen in hospitalized patients; disseminated via blood
What is haemophilus influenzae?
Small, coccobacillary gram-negative organism
Colonizes nasopharynx of normal individuals and lower airways of COPD patients
What is Klebsiella pneumoniae?
Large gram - bacillus
Found in GI tract
Seen in alcoholics
Causes thick, bloody, mucoid sputum (currant jelly sputum)
What is pseudomonas aeruginosa?
Gram - bacillus
Found in variety of environmental sources
Seen in debilitated, hospitalized patients previously treated wiht antibiotics
What is legionella pneumonphila?
Cause of pneumonia typically associated with water reservoirs
Gram - bacillus
Poorly stained ; affets healthy and prior respiratory defense deficient individuals
NOn-respiratory manifestations: GI, CNS, Hepatic, Renal
What is chlamydophila pneumoniae?
Obligate intracellular parasite
Not readily cultured
5-10% of pneumonias
What is mycoplasma pneumoniae?
Smallest organism identified; intermediate between virus and bacteria
10-20% of all pneumonias
“Walking pneumonia” -> chest xray looks worse than clinical presentation
What settings do anaerobic organisms cause pneumonia ins?
Aspiration of secretions (impaired consciousness due to coma, alcohol or seizures; or difficulty swallowing due to neuromuscular disease)
Poor dentition or gum disease are a risk factor (larger burden of organisms)
What is the pathology of pneumonia characterized by?
Infection and inflammation of distal pulmonary parenchyma
Influx of neutrophils, edematous fluid, erythrocytes, mononucelar cells, fibrin
What is bronchopneumonia?
Distal airway inflammation prominent along with alveolar disease
Spread of infection occurs through airways
Patchy distribution
E.g. staph aureus and gram - bacilli
What is lobar pneumonia?
Infectious process throughot entire lobe of lung (dense consolidation)
Spread via alveolus to alveolus and from acinus to acinus via interalveolar pores (pores of Kohn)
E.g. strept pneumo, klebsiella pneumoniae
What is interstitial pneumonia?
INflammatory process within interstitial walls rather than alveolar spaces
E.g. mycoplasma pneumoniae, influenza
What do we see here?
Bronchopneumonia
What do we see here?
Lobar pneumonia
What do we see here?
Interstitial pneumonia
How does pneumonia cause symptoms/disease?
Inflammaiton and infetion of distal air spaces leads to decreased ventilation
V/Q ratio decreased in diseased regions
If totally filled with inflammatory exudate, no ventilation : shunt -> hypoxemia
CO2 retention is not a common feature of pneumonia
Typically hyperventilate
What are symptoms of pneumonia?
Fever
Cough (productive or not)
Shortness of breath
Pleuritic chest pain if process extends to pleural surface
What do you find on exam in pneumonia?
generalized infection (tachycardia, tachypnea, fever)
Lung exam: opening/closing of distal airspaces = rales; consolidation = bronchial breath sounds, tactile fremitus, egophony, whisper pectorliquoy, dullness to percussion
What are differences in typical vs atypical pneumonia?
Typical = acute, productive cough, lung exams with signs of consolidation, leukocytosis with neutrophilia, CXR shows consolidation, bugs include strept pneumo, h. flu, klebsiella pneumoniae, staph aureous, anaerobes
Atypical = gradula, non-productive cough, normal WBC, systemic compalints more than respiratory, bugs include mycoplasma pneumoniae, chlaidophyla pneumoniae, legionella, viruses
What is histoplasmosis?
Histoplasma capsulatum
Dimorphic -> branching hyphae in soil, round, oval yeast in body
Mississippi or Ohio River Valley
Self limited in immunocompetent, lifethreatening in immunocompromised
COPD patients resembles tuberculosis
inhale sporesorganisms converts to yeast phaseinflammatory response in lung parenchymayeast may not be killed by macrophages and spreads to other organsdelayed hypersensitivity develops and immune response becomes granulomatous
What is coccidiomycosis?
Coccidiodes immitis
Dimorphic - spherules in tissue, mycelia ins oil
San Joaquin valley
Inflammatory response is granulomatous
Immunocompetent = self limited
Immunocompromised = hematogenous spread and disseminated disaese
Can resemble TB
What is blastomycosis?
Soil-dwelling blastomyces dermatidis
Midwestern and Southeastern US
Neutrophilic response but subsequently includes macrophages, and T cells; granulomas and pyogenic response
Resembles bacterial pneumonia
Self-limited
IMpaired immunity can be more rapid or severe disease
What is aspergillus?
Widespread
Aspergillus fumigtus most common
NOT dimorphic, always mycelia (branching hyphal form)
Everyone exposed
What is ABPA?
Allergic bronchopulmonary aspergillosis
Predisposing feature is asthma
Resides in airway and is important as antigen, not as pathogen
What is aspergilloma?
Predisposing feature is preexisting cavity within pulmonary parenchyma (e.g. due to TB)
COlonzies cavity with little invasion
Presents as hemoptysis or with no symptoms but found on CXR
What is invasive aspergillosis?
Predisposed by impaired immune resopnse
Invades and spreads through lung tissue
What is chronic necrotizing pulmonary aspergillosis?
Predisposing feature is underlying lugn disease or impairment of immune system
Indolent, localized invasion of parenchyma
Necrosis of involved tissue -> cavity formation
What do we see here?
Aspergilloma
What is pneumocystis jiroveci?
Causes pneumonia in malignancy, organ transplant, or AIDS
Insidious onset fever and dyspnea
Alveolar filling -> hypoxemai is prominent clinical feature
What are potential complications of pneumonia?
Abscess or empyema
What is a lung abscess?
Localized collection of pus
Results form tissue destruction
Neutrophil rich
Etiologic agents are bacteria that cause necrosis (anaerobes, staph aureaus, gram negs)
What is an empyema?
When pneumonia extends to pleural surface -> pus in pleural space
Thick, creamy or yellow fluid within space; enormous number of leukocytes and bacterial organisms
Need to drain and treat with antibiotics
What do we see here?
Lung abscess
What do we see here?
Empyema
How do we base antibiotic therapy in pneumonia patients?
Where it was acquired
How do we treat community acquired pneumonias?
Macrolides or doxycycline
Fluoroquinolone or β-lactam plus macrolide
How do you treat nosocomial pneumonia?
Complex, depends on particular pathogens that are common in hospital, etc.
What define bronchopneumonias?
Patchy consolidation of lung centered on bronchi
Neutrophils in bronchi, bronchioles, and adjacent alveolar spaces
What define lobar pneumonias?
Affect entire lung lobe but are rare now due to antibiotics
Still seen wiht particularly virulent organism or immunosuppressed host
What is the difference between bronchopneumonia and lobar pneumonia?
What do we see here?
Bronchopneumonia
What do we see here?
Lobar pneumonia
What is the cell type seen in acute bacterial pneumonia?
PMNs, RBCs and fibrin (neutrophils!!!)
What are symptoms of lung abscesses?
Cough
Fever
Foul-smelling sputum
Chest pain
Weight loss
How do you treat lung abscesses?
Antibiotics
Resection may be required
How does a lung abscess appear grossly?
Thick fibrotic walls and surrounding pneumonia in chronic abscesses
What do we see here?
Lung Abscess
What makes atypical pneumonias atypical?
Location of inflammation -> seen in alveolar septa and pulmonary interstitium (not in the airspaces)
Most commonly caused by mycoplasma pneumoniae, and viruses
Inflammation is comprised of LYPMHOCYTES, not neutrophils
What cell type characterizes atypical pneumonia?
Lymphocytes
What do we see here?
Atypical pneumonia (viral)
What are pulmonary viral infections?
CMV
Herpes I and II
Adenovirus
Influenza and parainfluenza
What do we see here?
Intranuclear and intracytoplasmic inclusions typical of cytomegalovirus
What do we see here?
Intranuclear and intracytoplasmic inlcusions typical of cytomegalovirus
What do we see here?
Intranuclear and intracytoplasmic inlcusions typical of cytomegalovirus
What do we see here?
Multinucleate cells with intranuclear inclusions typical of herpesviruses
What do we see here?
Single large intranuclear lesion characteristic of adenovirus infection (smudge cell)
What is a Gohn Complex?
Pulmonary granuloma and hilar lymph node involvement
What is miliary tB?
Disseminated TB resulting in multiple small granulomas and other organ involvement
What do we see here?
Gohn Complex : granuloma + hilar LN involvement
What are sites of tuberculous disease?
Lung
Meninges
Kidneys
Fallopian Tubes
Adrenals
Vertebrae
When do you see mycobacterium avium intracellulaire (MAI)?
HIV/immunocompromised
Right middle lobe syndrome (Lady Windemere syndrome)
Where is histoplasma located?
Mississippi + Ohio RIver Valey but also Carribean and Asia
What do we see here?
Histoplasma - narrow based budding
Where does coccidiodomycosis live?
Arizona, “San Joquin Valley”
What do we see here on PAS stain?
Coccidiomycosis
Where is blastomycosis live?
Deep south (Louisiana, Mississippi, etc)
WHich organism causes broad based bud?
Blastomycosis
What do we see here?
Broad based budding (blastomycosis)
What do we see here?
Aspergillosis
What do we see here?
Halo typical of cryptococcus
What is unique about cryptococcus?
Mucamine capsule, highlighted by DPAS, Aclian blue, or micicarmine
What do we see here?
Pink frothy material that is vacuolated space characteristic of PCP (Pneumocystis jirovecii)
How are TB granulomas formed? What molecules are important for this?
TNFα and IFNγ and other cytokines activate foam cells to form granuloma
Why may you get a false negative PPD?
Underlying disease with depressed cellular immunity
Why might you get a false positive PPD?
Past infetion with other non-tuberculous mycobacteria (have shared antigens)
What defines latent TB?
NAME?
What defines TB disease (active TB)?
Presence of clinically active disease in one or more organ systems with confirmation of MTB organism
What is primary tuberculosis?
Disease followign initial exposure
What is proressive primary TB?
Reflects primary disease that has not been controlled by hose defense mechanisms and continues to be actie beyond hypersensitivity
What is reactivation TB?
Disease that reactivates after a period of latency
What is reinfection TB?
Disease in previously infected person that results from exposure to another source of organisms
What is the characteristic location for reactivation of TB?
Apical regions of upper lobes, and to lesser extent, superior segment of lower lobes
High pO2 and less perfusion
How does TB present?
Systemic symptoms (non-specific): weight loss, anorexia, fatigue, low-grade fever, night sweats
Pulm: cough, sputum, hemoptysis
Abnormal CXR but no clinical symptoms
How do you diagnose TB?
Stained smears
Nucleic acid amplification
Culture (need for drug susceptibility testing)
Who gets infected with non-TB mycobacteria?
Those iwth underlying lugn disease in which lung defenses are presumably diminished
AIDS
