Kit Delgado – mcd2027@columbia.

edu

Clinical Pulmonary Pathophysiology

Obstructive Disease
Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Asthma ¾ Hyperinflation, ¾ PaO2 down Spirometry (Obstructive) Ventilatory Capacity and Mechanics Bronchodialators
otherwise during attack ¾ During attack all ¾ Bronchospasm increases resistance in all ¾ Some open
normal ¾ PaCO2 indices of expiratory airways airways at mild
¾ Dyspnea, normal or low flow are significantly ¾ Increased RV caused by premature airway expense of
orthopnea, until late in reduced closure during full expiration decreasing PaO2
anxiousness. May disease ¾ FVC also reduced ¾ High TLC has advantage of reducing slightly. From
be sustained in late because the airways resistance by increasing radial traction of relief of
phase. close prematurely airways vasoconstriction of
towards the end of a full poorly ventilated
¾ Allergy or non- expiration Gas exchange areas.
allergy ¾ Pc20: 20% fall in FEV1 ¾ Arterial hypoxemia common – caused by
when administered V/Q mismatch. Uneven ventilation. Corticosteroids
¾ Rapid pulse, pulsus irritant
paradoxus (fall in ¾ Physiological dead space and shunt high. Candidate target
pulse pressure Flow-volume curve: But no pure shunt, surprising considering molecules for new
during inspiration) ¾ Typical obstructive there is mucus plugging (Probably from therapies:
may be present pattern, but no scooped collateral ventilation). ¾ mAb Ige
out appearance ¾ LTD4
Pathogenesis: Diffuse ¾ PaCO2 prevented from rising by increasing ¾ PGD2
Disease of Conducting Static Lung Volumes: ventilation to alveoli in face of V/Q mismatch ¾ PAF
Airway ¾ Increased during attack (stimulation of peripheral chemo receptors by ¾ Substance P
(RV, FRC very high) mild hypoxemia or by intrapulmonary ¾ MBP, ECP
¾ FRC measurement receptors) ¾ Ach
value (body ¾ Mast cell
plesthysmography> ¾ Status asthmaticus: PaCO2 rises Æ pH falls secretory
helium dilution) Æ sign of impending respiratory failure. products: serine
Need mechanical ventilation. protease tryptase
¾ Diffusion capacity normal
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Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Cystic Firbosis CXR: ¾ Increasing Spirometry ¾ A-a gradient widened Treatment:
¾ can look fairly hypoxemia ¾ FEV1 starts going down ¾ Compliance down ¾ Antibiotics
¾ Child normal beginning in in moderate to severe ¾ Flow rates at low volumes down (aerosolized key)
¾ cough ¾ hyperinflation mild disease disease ¾ Slope of phase III nitrogen washout up ¾ Airway clearance
¾ sputum ¾ as disease ¾ FEF25-75 starts going ¾ Physiological dead space up (chest physical
¾ weight loss progresses down in mild disease ¾ Exercise tolerance down therapy, flutter
¾ School/work Æ ¾ These do not improve device, DNAase -
absenteeism bronchiectas with bronchodialators! mucolytic, anti-
Complications
¾ Dyspnea is inflammatory)
¾ Atelctasis
¾ Decreased exercise ¾ older pts. Æ Lung volumes ¾ Nutrition
¾ Hemoptysis
tolerance pneumothora ¾ VC starts going down in
¾ Pneumothorax
¾ Crackles x moderate disease
¾ Clubbing ¾ Increasing RV/TLC ¾ Cor Pulmonale
¾ Kyphosis CT: beginning in mild
¾ looks much disease
Pathogenesis: Diffuse more
Disease of Conducting abnormal
Airway than CXR

Bronchoscopy:
¾ mucus in
airways
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Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
COPD ¾ Marked ¾ PaO2 slightly Spirometry (Obstructive): Ventilatory Capacity and Mechanics
Emphysema Type A chest depressed ¾ FEV1 reduced ¾ Airways close prematurely at abnormally high
(“Pink Puffer”) expansion ¾ PaCO2 ¾ FEV1/FVC reduced lung volume
¾ Increasing dyspnea ¾ Translucent normal ¾ FEF25-75: reduced ¾ Elastic recoil: reduced in emphysema Æ
over years lungs increase in TLC; normal in Bronchitis
¾ Little or no cough ¾ Attenuated Flow volume curve: ¾ Airway resistance: increased
¾ No cyanosis peripheral ¾ expiration: grossly
¾ Quiet breath sounds vessels abnormal, “scooped Gas exchange
¾ Normal Jugular out appearance” ¾ V/Q mismatch inevitable, with or without
venous pressure ¾ inspiration fairly normal CO2 retention. Due to disorganization of
lung architecture Æ uneven ventilation, and
Pathogenesis : Lung Volumes: uneven blood flow. Compensated for by
Destruction of Alveolar ¾ FVC reduced collateral ventilation and hypoxic
Wall ¾ TLC, RV, FRC vasoconstriction.
increased ¾ A-a gradient always increased, esp. in
¾ Value on body patients with chronic bronchitis
plesmography > gas
dilution (slow ¾ Dead space particularly increased in
equilibration process in emphysema
Chronic Bronchitis poorly ventilated areas)
(+Emphysema) Type B ¾ Shunt seen in chronic bronchitis
(“Blue Bloater”)
¾ increasing dyspnea ¾ No diffusion abnormality in emphysema
over years ¾ Normal ¾ PaO2 very
¾ frequent cough ¾ Moderate or low ¾ On exercise, the PaO2 may fall or rise –
with sputum no increase in ¾ PaCO2 often depending on ventilation or cardiac response
¾ often cyanosis chest volume raised
¾ May have rales, ¾ If PaCo2 rises, pH will fall Æ Resp. acidosis.
rhonci May be compensated for by retaining bicarb in
¾ May have raised chronic conditions.
JVP
¾ May have Pulmonary Circulation
peripheral edema ¾ Pulmonary artery pressure may rise with
severe disease (destruction of pulmonary
Pathogenesis: Diffuse vasculature; hypoxic vasoconstriction)
Disease of Conducting ¾ Cor pulmonale --> RV dilation (esp. in Type B
Airway patients)

Control of Ventilation
¾ One reason for CO2 retention Æ increased
work of breathing due to increased
resistance
¾ Minute ventilation increased
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Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Tracheal Obstruction ¾ PaO2 down Flow-Volume Curve Hypoventilation No response to
¾ PaCO2 up ¾ abnormal expiration bronchodialators
Inspiratory and AND inspiration
expiratory stridor from:
¾ Inhaled foreign
body, or
¾ Stenosis after
indwelling
tracheaostomy
tube, or
¾ Compression by
enlarged thyroid

Bronchial Obstruction ¾ In inhalation ¾ PaO2 down ¾ Adminster 100% O2 Æ ¾ Absorption atelectasis may occur (b/c sum
of object, look at A-a gradient = of partial pressure in mixed venous blood less
¾ Inhalation of foreign Right lung most sensitive test than in alveolar gas)
body (size of affected ¾ Perfusion of unventilated lung Æ reduced
peanut), or more than by hypoxic vasoconstriction
¾ Bronchial tumor, or left (due to ¾ Infection may follow localized obstruction Æ
¾ Enlarged more direct lung abcess
surrounding LN path from
trachea)
¾ Enlarged LN,
also more
likely to cause
obstruction
on right
(anatomy)
¾ Collapsed
lobe may be
visible
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Restrictive Disease
Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Interstitial Lung ¾ Alveolar ¾ PaO2 and Spirometry (Restrictive): Ventilatory Capacity and Mechanics
Diseases filling PaC02 are ¾ FVC reduced ¾ Findings consistent with fibrosis of alveolar
¾ Interstitial reduced and ¾ FEV1/FVC = normal, or walls
Signs, Sx: infiltrates: pH is normal high ¾ Stiff lungs with decreased expansile
¾ Dyspnea with linear; ¾ Hypoxemia ¾ FEF25-75 = normal, or capacity; airway resistance normal
exertion nodular; mild at rest high (reduced lung volumes, preservation of flow
¾ Persistent, non- reticulonodula until disease is rates, small tidal volumes, resting tachypnea)
productive cough r; honeycomb advanced or Flow-volume curve: ¾ Very negative intrapleural pressure at TLC
during ¾ downslope = higher than
Hx: exercise normal Gas Exchange
¾ Occupational, Drug, ¾ Elevated A-a gradient
Family history, Lung Volumes:
Respiratory, illness, ¾ All are reduced, relative At rest:
Non-resp. illness proportions preserved ¾ V/Q mismatch primary cause of hypoxemia
(1 b/c transit-time enough Æ diffusion =
PE: Pressure-Volume Curve: normal, 2 b/c disorganization of the
¾ Tachypnea ¾ Displaced downward architechture)
¾ Tachycardia ¾ Low PaCO2 caused by increased
¾ Crackles DLCO ventilation (tachypnea)
¾ Clubbing ¾ Reduced ¾ Arterial pH normal or high, may fall in
respiratory failure
Pathogenesis: Diffuse Exercise:
thickening of alveolar ¾ V/Q mismatch + diffusion impeded (not
wall enough time for gas transit to capillary)
¾ High ventilation Æ PaO2 fall, PaCO2 fall Æ
respiratory alkalosis

Pulmonary Circulation
¾ Increased pulmonary vascular resistance
especially during exercise – due to interstitial
fibrosis

Control of Ventilation
¾ Increased traction of airways of lung may
cause J-receptors to fire Æ
¾ Increased work of breathing- compensated
for tachypneic brathing - reduced maximal
voluntary ventilation
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Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Pneumonia ¾ Opaque ¾ PaO2 down Spirometry: Ventilatory Capacity and Mechanics
blotches, ¾ PaCO2 down ¾ Resistance to air flow ¾ Reduced compliance and filling of air
once there’s unaltered spaces with fluid, Æ decreased lung volumes
Pulmonary (alveolar
fluid replacing ¾ Minute and alveolar ventilation increased by
edema)
air in the Lung Volumes J-receptor stimulation and hypoxemia
alveoli ¾ Decreased
Pulmonary
Gas Exchange
hemmorhage
Administered 100% 02 ¾ PaO2 reduced due to increase in
¾ Doesn’t raise PaO2! physiological shunt. (Due to replacement of
Hyaline membrane
alveolar air with fluid).
disease of newborn
¾ PaCO2 reduced because of compensatory
hyperventilation
Pathogeneis: Diseases
¾ V/Q mismatch, and diffusion problems do
of the Acini and
not play a role in these diseases
Intersitium

Pulmonary embolism ¾ PaO2 down Ventilatory Capacity and Mechanics

¾ PaCO2 down Changes may occur immediately
Risk factors: vein wall ¾ Compliance: Falls within a minute.
injury, stasis, Characteristic of uneven distal airway
hypercoagulability constriction. (Same mediators as
vasoconstrcition).
Sx: Dyspnea, tachypnea,
sometimes expiratory ¾ Alveolar stability: aveoli closing distal to
wheezes airway constriction further reduce compliance

Small emboli: Small: ¾ Airway resistance: airways that ventilate

¾ Frequently ¾ Right totally occluded vessel Æ see very low
unrecognized ventricular PaCO2 Æ vagal mediated
¾ Repeated emboli hypertrophy bronchoconstriction Æ increase in airway
may result in (after resistnace Æ wheezing in some patients
pulmonary repeated
hypertension (2%) emboli Æ ¾ Dyspnea: from increased work of breathing
pulmonary due to decreased lung compliance (major),
hypertension) and increased airway resistance (minor)

¾ Ventilation: Tachypnea – rapid shallow

Medium-sized emboli Medium breathing caused by J-receptor stimulation
¾ Sometimes pleuritic ¾ Normal (not from chemorector mediated hypoxemia –
pain, dyspnea, ¾ May see this contributes to dyspnea).
slight fever shadow of
¾ Hemoptysis infarction Gas Exchange
¾ Pleural friction rub Hypoxemia develops rapidly. A-a gradient
widening proportional to magnitude of embolic
Massive emboli event.
¾ Hemodynamic
collapse with shock, ¾ V/Q mismatch = major reason.
pallor, central chest Heterogeneous distribution of ventilatory
pain abnormalities

¾ Shunt: continued ventilation of unperfused

areas accounts for 1/3 of A-a gradient

¾ Hypotension with
rapid weak pulse,
and JVP increase
¾ Sometimes fatal
Sustained Pulmonary ¾ RV
Hypertension
Progressive dyspnea
with episodes of syncope
during exertion
From:
Increase in LAP
Increase in Pulmonary
blood flow (ex.
Congenital heart
disease)
Increase in pulmonary
vasculature resistance
lung disease:
¾ Vasoconstriction
(V/Q mismatch :
chronic bronchitis,
CF, acute
bronchiolitis,
asthma ;
Hypoventilation)
¾ Anatomic
Restriction:
(Extravascular:
ILD’s; Intravascular:
pulmonary
vasculitis, schisto,
filariasis, tumor
emboli, sickle cell)
st
¾ Combo of two: (1
group: emphysema,
healed TB,
nd
anthrosilicosism; 2
group: PE)
7
widening.
¾ Diffusion: doesn’t play a role.
¾ Low PaCO2 from hyperventilation Æ
respiratory alkalosis (from activation of
irritant and J-receptors).
Pulmonary Circulation
¾ Pulmonary hypertension (mechanical
obstruction + release of vasoactive
substances - Histamine).
Right Ventricle
¾ In massive embolus Æ immediate dilation,
possibility of failure
¾ PaO2 normal ¾ Ventilatory tests Ventilatory Capacity and Mechanics:
hypertrophy or low usually normal Dyspnea with exertion
¾ PaCO2 low if ¾ Lung compliance: decreased
hyper- progressively as the hypertensive process
ventilating intensifies
¾ Airway resistance: not increased during this
process
¾ Ventilation: Tachypnea – rapid shallow
breathing – during exertion.
Gas Exchange:
Moderate widening of the A-a gradient.
¾ Diffusion Abnormality: major cause of
hypoxemia (from underlying interstitial
abnormalities and arteriopathy).
¾ As the flow through pulmonary vasculature
becomes limited Æ drop off in CO Æ syncope
Pulmonary Circulation
¾ Loss of microcirculation and arteriopathy b/c
increase of resistance to flow
¾ May result in systemic levels of blood
pressure in pulmonary vasculature bed
Right Ventricle
¾ RV hypertrophy increases with sustained and
progressive pulmonary hypertension
¾ Drops in CO may lead to syncope, chest pain
¾ Tachyarrthmias and sudden death are
common
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Acute Respiratory Failure
Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Acute Hypoxic ¾ Low PaO2 V/Q mismatch ¾ Treat airway
Respiratory Failure ¾ Normalized ¾ Most common etiology of depressed PaO2 obstruction and/or
(AHRF – Type 1) PaCO2 clinically chest infection

“Water, blood, or pus” Increased Shunt Flow ¾ Administration of

Æ air space flooding Æ ¾ This is the major gas exchange long-term O2
Increase in Shunt flow abnormality of ARDS (can be viewed as therapy often
extreme V/Q mismatch. However, results in required
admixture of blood that isn’t ventilated at all Æ
therefore won’t respond to 100% O2.)
From fluid filled alveolar spaces.

Diffusion Abnormality
¾ Even when it exists, contribution to hypoxia is
negligible unless it falls below 20%. This level
of dysfunction could play a role in ARDS and
COPD

Alveolar Hypoventilation
¾ If no widening of A-a gradient, then not a gas
exchange abnormality as above.

Ventilatory Respiratory ¾ Low PaO2 Respiratory drive dysfunction: ¾ Often responds to

Failure (Type II) ¾ High PaCO2 ¾ Drug OD, CVA, tumor, peripheral receptor general measures
dysfunction directed at the
Increased load, ¾ Misuse of O2 therapy: (ex. COPD patient airway obstruction
increased effort, developed CO2 retention over several months or infection
decreased drive Æ Æ compensated respiratory acidosis Æ
decrease in ventilation therefore respiratory drive now from ¾ Mechanical
hypoxemia Æ gets infection Æ given 100% ventilation
O2 Æ abolishes drive Æ 100% O2 frequently
discontinued Æ profound hypoventilation.) required
(Can also get worsening of the V/Q
mismatch with lifting of hypoxemic
vasoconstriction).

Neuromuscular disease
¾ Guillan-Barre, MG, polio, spinal trauma,
botulism, ALS, myositis

Chest Wall/Pleural Disease

¾ Trauma (flail chest), kyphoscoliosis, massive
pleural effusion, pneumothorax

Airway obstruction
¾ Upper airway, stenosis, tumor

Peripheral airway disorders

¾ Asthma, anaphylaxis, COPD, CF, foreign
body
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Clinical Presentation Chest Imaging Labs / Blood Pulmonary Function Tests Pathophysiology Mechanisms Management
Gases
Adult Respiratory ¾ Clouding ¾ Both fall Ventilatory Capacity and Mechanics ¾ Ventilator with
Distress Syndrome seen in chest drastically 2 ¾ Lung becomes very stiff (alveolar edema) high FIO2
radiograph Æ days after ¾ Decreased lung volume
Associated with some progresses incident -
severe underlying to uneven PaO2 (40), Gas Exchange
medical or surgical opacification PaCO2 (20) ¾ Marked V/Q mismatch Æ Increase in Shunt
illness not connected flow (50% or more)
to the lung (ex. ¾ Must be put on ventilator with high FIO2 Æ
Hemorrhagic shock after prognosis not good when high shunt flow
accident Æ treated with present
fluid replacement) ¾ Stimulation of J receptors allows for
compensatory hyperventilation
2 days following
trauma Æ increase in
RR and fall in PaO2,
PaCO2 Æ severe
hypoxemia Æ mortality
50%

Pathogenesis: diffuse
alveolar damage Æ
alveolar capillary
permeability