Respiratory (04)

Pathology of Pulmonary
Vascular Diseases
January 12, 2015
Dr. Geiss

Normal arteries

ELASTIN STAIN

ELASTIN STAIN

Pulmonary vascular
diseases
Pulmonary edema
Pulmonary embolism and
infarction
Pulmonary hypertension
Diffuse pulmonary hemorrhagic
syndromes

Pulmonary vascular
diseases

Pulmonary edema: causes

Hemodynamic disturbances
hemodynamic (cardiogenic)
pulmonary edema
Microvascular injury
increased microvascular permeability

Pulmonary embolism and infarction

Pulmonary hypertension
Diffuse pulmonary hemorrhagic
syndromes

Hemodynamic pulmonary
edema

Etiologies

increased hydrostatic pressure

left-sided heart failure
(cardiogenic pulmonary edema)
other (uncommon)

decreased oncotic pressure

(uncommon cause of pulmonary
edema)

Morphology
acute: congestion
septal (interstitial) edema
alveolar edema (transudate)
alveolar microhemorrhages

chronic: brown induration

(heart-failure cells fibrosis)

Complications
impaired respiratory function

Edema due to microvascular injury

Focal: pneumonia
Diffuse:
acute (adult) respiratory distress syndrome
(ARDS)
Synonym: noncardiogenic pulmonary edema
Characteristics
abrupt onset
severe hypoxemia
diffuse pulmonary infiltrates

absence of heart failure or fluid overload

Classification (based on PaO2/FIO2 ratio)

mild
moderate
severe

 Etiologies

ARDS

Direct injury to lungs

diffuse pneumonia (esp. viral)

aspiration of gastric contents
inhalation: toxic gases, smoke, other irritants
near-drowning
oxygen toxicity/prolonged mechanical ventilation
radiation

Systemic disorders
SEPSIS
trauma/burns
metabolic disorders (e.g., pancreatitis, uremia)
drugs (esp. cytotoxic)
SHOCK DUE TO ANY CAUSE (SHOCK LUNG)

Morphology: diffuse alveolar damage (DAD)

The alphabet soup of shock

Systemic acute inflammatory syndrome (SIRS)
Disseminated intravascular coagulation (DIC)
Diffuse alveolar damage (DAD)
Acute respiratory distress syndrome (ARDS,
shock lung)
Acute tubular necrosis (ATN)
Acute renal failure (ARF)
Multiple organ failure (MOF),
a.k.a. Multiple organ dysfunction syndrome (MODS)

Diffuse alveolar
damage (DAD)
Pathogenesis:
diffuse damage to the
alveolar-capillary
membrane

Diffuse alveolar damage (DAD)

Pathogenesis: diffuse damage to alveolar-capillary membrane

Morphology of ARDS:
Diffuse alveolar damage
(DAD)

Gross

heavy (up to 5x normal

weight)
red
firm
essentially airless

Microscopic
exudative phase
congestion, edema,
inflammation
hyaline membranes
(black arrows)
exuded plasma proteins
necrotic epithelial
cell debris

Diffuse alveolar
damage (DAD)

Resolution
granulation tissue
formation
granulation tissue
resolution
return to normal
architecture
AND/OR

Proliferative phase
type II pneumocyte
hyperplasia
(blue arrows)
fibrosis (organization)
intra-alveolar
interstitial (black
arrows)

ARDS (clinical, radiologic)

Respiratory insufficiency (dyspnea,
tachypnea)
Severe arterial hypoxemia
(cyanosis), refractory
to O2 therapy
Radiograph: diffuse bilateral
infiltrates extensive
opacification (white-out)
Decreased lung compliance
Complications
(due to hypoxia)
multisystem organ failure
death

DAD: outcome
Resolution AND/OR
Fibrosis (organization)
interstitial fibrosis
+ honeycombing

Treatment
underlying disease
supportive care

Prognosis
survival: ~60%
causes of death
sepsis
multiorgan failure
direct lung injury

Acute interstitial pneumonia (AIP)

Synonym: Hamman-Rich syndrome
Definition:
idiopathic DAD
presents in proliferative
phase
often progresses
to organization

Acute respiratory failure

( antecedent upper
respiratory infection)
Prognosis
~35-75% fatal, usually
within 1-2 months
survivors
residual chronic lung disease (interstitial fibrosis)
recurrences

Pulmonary thromboembolism
Large-vessel pulmonary thrombosis is rare
Origin of emboli
deep veins, lower extremity (95%)
pelvic veins

Predisposition
immobility
hypercoagulable state (thrombophilia)

Outcome
clinical silence: 60-80% of cases
60% compromise sudden death (5% of cases)
acute respiratory compromise
acute cor pulmonale

pulmonary infarction (10% of cases)

recurrence: common (30% of cases)
pulmonary hypertension
(multiple emboli over time)
passage to systemic circulation
(paradoxical embolism)

SADDLE EMBOLUS

Pulmonary
thromboembolism

ACUTE THROMBOEMBOLUS

Large-vessel pulmonary thrombosis rare

Origin of emboli
deep veins, lower extremity (95%)
pelvic veins

Predisposition
immobility
hypercoagulable state (thrombophilia)

Outcome

clinical silence: 60-80% of cases

60% compromise sudden death
pulmonary infarction (10% of cases)
recurrence: common (30% of cases)
pulmonary hypertension
(multiple emboli over time)
passage to systemic circulation
(paradoxical embolism)

ORGANIZED THROMBOEMBOLUS

(paradoxical embol

via cardiac septal defect

rare

ELASTIC STAIN

Pulmonary hypertension (PH)

Definition sustained mean pulmonary

arterial pressure at rest of 25 mm Hg
(ULN: 20 mm Hg)
Principle mechanisms

pulmonary blood flow and/or pressure

pulmonary vascular resistance
left heart resistance to blood flow

Clinical classification (WHO)

1.
2.
3.
4.
5.

Pulmonary arterial hypertension (PAH)

PH due to left heart failure
PH associated with lung diseases/hypoxemia
Chronic thromboembolic PH
PH due to unclear mechanisms

1. Pulmonary arterial hypertension (PAH)

Idiopathic (primary) PAH
Heritable (familial) PAH
mutations in bone morphogenetic protein
receptor type 2 (BMPR2) signaling pathway
normal: inhibition of vascular EC and SMC
dysfunction and proliferation
mutation: intimal, medial thickening
modifier genes/environmental triggers

other mutations

Drug- and toxin-induced PAH, e.g.:

fenfluoramine/phenteramine (fen phen)
methamphetamine

PULMONARY
ARTERIAL
PULMONARY
ARTERIAL
HYPERTENSION
HYPERTENSION

PAH associated with, e.g.:

connective tissue diseases (esp. systemic sclerosis)

congenital heart diseases
schistosomiasis
persistent PH of the newborn (PPHN)

Pulmonary hypertension (PH)

2. PH due to left heart disease
systolic or diastolic dysfunction
left atrial pressure
pulmonary venous pressure
pulmonary arterial pressure (PH)

valvular disease,
e.g. mitral stenosis ( left atrial pressure)

3. PH associated with lung

diseases/hypoxemia
chronic obstructive lung disease (COPD)
chronic restrictive lung disease

Pulmonary hypertension (PH)

4.

5.

Chronic thromboembolic PH
functional cross-sectional area
of pulmonary vascular bed
in pulmonary vascular
resistance
pulmonary hypertension
PH due to unclear mechanisms (miscellaneous)
hematologic disorders
systemic disorders
metabolic disorders
others

Pulmonary hypertension:
morphology

Main pulmonary arteries: atherosclerosis

Frazier A A et al. Radiographics 2000;20:491-524

2000 by Radiological Society of North America

Pulmonary hypertension: morphology

(muscular arteries, arterioles)
Low grade (potentially reversible)
intimal thickening fibrosis
medial hypertrophy

NOT
NORMAL

H&E STAIN;
REMAINING SLIDES
STAINED FOR ELASTIN
(BLACK)

Pulmonary hypertension:
morphology
(muscular arteries, arterioles)
High grade (irreversible)
plexogenic pulmonary
arteriopathy
plexiform lesions
angiomatoid lesions

fibrinoid necrosis

Pulmonary hypertension: course

Idiopathic and heritable PH
respiratory distress
cyanosis
right ventricular
hypertrophy
fatal cor pulmonale
(80% within 2-5 yrs)
treatment
current
vasodilators
heart-lung transplant
future: gene therapy
(heritable PAH)

Other forms of PH:

course and
treatment vary with
underlying disease

Diffuse pulmonary
hemorrhagic
syndromes
Synonym: diffuse alveolar
hemorrhage (DAH)
Syndromes
Goodpasture syndrome
Idiopathic pulmonary
hemosiderosis (IPH)
Vasculitis-associated
pulmonary hemorrhage

Goodpasture
syndrome

Etiology: anti-basement
membrane antibodies
(autoimmune)
Epidemiology
male predominance
2ND 3RD decade
associated with renal
disease (RPGN)

Morphology
inflammatory

destruction of
basement membrane
immunofluorescence:
pattern

linear
ANTI-BASEMENT MEMBRANE ANTIBODY

Idiopathic
pulmonary
hemosiderosis
(IPH)
Epidemiology
Predominantly
young children
Adult cases reported

Etiology
No antibody identified
Favorable response to
immunosuppressives
indicates possible
immune mechanism

Vasculitis-associated
pulmonary
hemorrhage
Associated conditions
microscopic polyangiitis (MPA)
(hypersensitivity vasculitis)
granulomatous polyangiitis
(GPA) (Wegener)
systemic lupus erythematosus

Lesion:
neutrophilic capillaritis
Prognosis: depends upon
underlying condition

Vasculitis-associated
pulmonary hemorrhage
Associated conditions
microscopic polyangiitis
(hypersensitivity vasculitis)
GPA (Wegener )
systemic lupus erythematosus
immunofluorescence:
granular pattern
EM: immune complexes in alveolarcapillary membrane (black arrow)

Lesion: neutrophilic capillaritis

Prognosis: depends upon
underlying condition

Pulmonary vascular
diseases
Pulmonary edema
Pulmonary embolism and
infarction
Pulmonary hypertension
Diffuse pulmonary hemorrhagic
syndromes