Twenty One Flashcards
What is atelectasis? What are some possible results of it? Describe four different types of atelectasis. What causes each to occur? Which ones are reversible? Which way does the mediastinum shift in each?
Atelectasis describes a reduction in lung volume due to incomplete
expansion of airspaces or, more commonly, the collapse
of previously inflated pulmonary parenchyma. In atelectasis,
perfusion of such nonventilated lung creates a physiological
shunt that mixes inadequately oxygenated blood from pulmonary
arteries with better oxygenated blood in the pulmonary
veins (Chap. 9). If the ventilation-perfusion mismatch is sufficiently
severe, systemic hypoxemia results. Additionally,
atelectatic lung is more likely to become infected.
Atelectasis can be subdivided by its pathogenesis.
In resorption atelectasis (also known as obstruction
atelectasis), air is prevented from reaching distal airspaces
because of airway obstruction. Then, as more distal
air is absorbed, the previously expanded lung collapses. The
extent of involvement is determined by the level of obstruction:
Obstruction of a major airway can result in collapse of
an entire lobe. Most commonly, a mucous or mucopurulent
plug is responsible for the obstruction, although any physical
obstruction will suffice. In resorption atelectasis, the mediastinum
shifts toward the affected side.
In compression atelectasis (also known as passive
atelectasis and as relaxation atelectasis), accumulation of
space-occupying material within the pleural space mechanically
compresses the lung parenchyma (Fig. 26.1). Compression
atelectasis complicates pleural effusion and pneumothorax
(see below), as well as pleural tumors (Chap. 31). Additionally,
compression atelectasis of basal lung zones complicates peritoneal
effusion (ascites) and frequently occurs in bedridden
patients due to diaphragmatic elevation. In compression
atelectasis, the mediastinum shifts away from the affected side.
Microatelectasis complicates adult and neonatal respiratory
distress syndromes (Chaps. 23 and 39) as well as interstitial
inflammatory lung diseases (Chap. 23). Its pathogenesis
involves a complex set of events, the most important being
deactivation of surfactant in the mature lung or its inadequate
synthesis in neonatal lung.
In the setting of localized or generalized pulmonary
fibrosis, the foci of fibrosis contract largely due to the action of myofibroblasts, collapsing adjacent lung tissue and resulting in contraction atelectasis or cicatrization atelectasis.
Generally, resorption atelectasis, compression atelectasis,
and microatelectasis are reversible, while contraction atelectasis
is not.
What is pulmonary edema? Generally, what causes it? List some specific causes as well as how common they are.
When edema develops in the lung, the excess fluid rapidly
moves from the interstitium to the airspaces (Chaps. 7 and 28).
While there are many specific causes of pulmonary edema
(see Table 7.2), it is generally due to a change in hemodynamics
(perfusion vs interstitial pressures) or to microvascular injury.
Congestive heart failure is the most common cause of an
increase in pulmonary venous pressure and the resultant pulmonary
edema. Less commonly, reduction of plasma oncotic
pressure will result in egress of fluid from the vascular space
into the interstitium and then the alveoli. Alternatively, an
increase in the permeability of capillaries, as occurs in the setting
of alveolar and microvascular injury, can result in edema
(Chap. 28).
Describe the gross and microscopic histology of pulmonary edema. What differences are there when it is due to elevated pulmonary venous pressure?
Gross manifestations of pulmonary edema include increase
in lung weight and a wet cut surface with frothy fluid visible
in larger airways. Microscopically, pulmonary edema is
characterized by pale, eosinophilic, glassy or finely granular intra-alveolar precipitate [Fig. 26.2 (a)]. In the setting of pulmonary
edema secondary to elevation of venous pressure,
alveolar septal capillaries will show congestion characterized
by engorgement with blood. Due to the delicate nature of alveolar
septa, congestion is typically accompanied by occasional rupture of capillaries, resulting in microhemorrhages that
release formed blood elements into alveolar spaces. As erythrocytes
are cleared by macrophages, hemoglobin is progressively
catabolized to hemosiderin, which persists in macrophage
cytoplasm. Thus, the presence of hemosiderin-laden macrophages
(or siderophages) reflects remote hemorrhage and
implies chronic congestion [Fig. 26.2 (b)]. While any form
of pulmonary hemorrhage will eventually show siderophages,
the most common cause of pulmonary congestion and hemorrhage
is congestive heart failure. This has led to widespread
usage of the term “heart failure cells” to describe such intraalveolar
hemosiderin-laden macrophages.
What are is pulmonary embolus? What is the most common cause? What are some risk factors for this?
A large majority of pulmonary emboli are thrombotic in origin.
Therefore, unless otherwise specified, the term “pulmonary
embolus” typically refers to pulmonary thromboembolus.
Pulmonary thromboembolism is involved in approximately
10% of hospital deaths. In more than 95% of cases, the source
of pulmonary thromboemboli is a thrombus in a deep vein of
the lower extremity (Chap. 27). Risk factors for venous thrombosis
and pulmonary thromboembolus include prolonged bed
rest (especially in the setting of lower extremity immobilization),
severe trauma, burns, congestive heart failure, and
hypercoagulable states (Table 26.1).
What are some primary causes of hypercoagulable states? Secondary causes?
Primary
Antithrombin III defi ciency Protein C defi ciency Defective fi brinolysis Factor V Leiden Prothrombin 20210A Hyperhomocysteinemia Antiphospholipid syndrome
Secondary
Obesity Recent surgery Pregnancy Oral contraceptive with high estrogen content Cancer
Describe how a pulmonary thromboembolus proceeds and what its complications are.
When a venous thrombus embolizes, it travels in progressively
larger systemic veins toward the right heart. Upon
ejection from the right ventricle, fragments of the embolism move into progressively smaller branches of the pulmonary
artery until they reach vessels too small to allow passage. At
that point the thromboemboli occlude a pulmonary artery
or arteriole and increase pulmonary vascular resistance and
can induce vasospasm. When a major vessel is occluded, the
resulting pulmonary hypertension can reduce cardiac output
and induce cor pulmonale and death. If death does not
result, pulmonary thromboembolism results in hypoxemia
due to ventilation-perfusion mismatch with increased dead
space ventilation (Chap. 8). The ischemia may also reduce
surfactant release and cause pleuritic pain that add to the work
of breathing (Chaps. 5 and 6). Despite the lung’s systemic
blood supply (Chap. 2), pulmonary thromboembolism can
result in lung parenchymal ischemia and pulmonary infarction.
In patients with patent foramen ovale (~30% of all people), pulmonary arterial thrombotic occlusion can cause
right-to-left shunting and subsequent paradoxic embolism,
in which a venous thrombus enters and embolizes systemic
arteries and cause distal ischemia.
What is the gross appearance of a thromboembolus? Microscopic? What is the gross appearance of a lung infarct? Microscopic?
Grossly, a pulmonary thromboembolus is a serpentine blood
clot impacted in a pulmonary arterial branch [Fig. 26.3 (a)].
A very large thromboembolus occluding the main pulmonary
arteries is typically referred to as a “saddle embolus.” Microscopically,
the thromboembolus is characterized by alternating
layers of fibrin (eosinophilic) and erythrocytes. Ischemic lung
damage is characterized by intra-alveolar hemorrhage [Fig.
26.3 (b)]. A pulmonary infarct will be conical (or, on cut section,
wedge-shaped) and hemorrhagic [Fig. 26.4 (a)]. Initially,
the infarct is red-blue. It becomes paler and later red-brown as
erythrocytes lyse and hemoglobin is degraded to hemosiderin.
Next, as fibroblasts progressively replace necrotic tissue with
scar, the infarct shows a gray-white peripheral zone. Microscopically,
infarcted lung tissue shows coagulative necrosis
with loss of nuclear basophilia, although alveolar hemorrhage
often dominates the microscopic appearance [Fig. 26.4 (b),
(c)]. In cases of sudden death due to saddle embolus, there are
typically no gross or microscopic changes to the lung.
Clinically, what happens with pulmonary emboli? What is the risk of a recurring pulmonary embolism? What can they result in? How are pulmonary embolisms treated?
Clinically, 60%-80% of pulmonary thromboemboli are
asymptomatic; approximately 5% cause acute cor pulmonale,
shock, or sudden death; and 10%-15% affect medium-sized
arteries and, through an unknown mechanism, cause dyspnea.
In the presence of an underlying risk factor, a patient who
has had pulmonary thromboembolism has a 30% chance of
recurrent pulmonary thromboembolism. A minority (< 3% of
patients with recurrent pulmonary thromboembolism develop pulmonary
hypertension (see below), chronic cor pulmonale, vascular sclerosis, and worsening dyspnea. Treatment of pulmonary
thromboembolism involves thrombolysis and anticoagulation.
If anticoagulation is contraindicated or not sufficient, a
filter (Greenfield filter, umbrella) can be placed in the inferior
vena cava; thromboemboli caught in the filter will undergo
fibrinolysis.
Aside from thrombi, what are some other causes of pulmonary embolisms? What are the effects?
In addition to venous thrombi, the student should remember
that embolism of the lung can be caused by air, bone marrow,
fat, foreign bodies, and amniotic fluid. In most instances,
the hemodynamic effects from such materials resemble those
caused by thrombi (Chap. 27). However, the duration of such
effects and the severity of pulmonary compromise they cause
may be transient (as for the nitrogen in air), or may persist
(as has been noted for crystals of talcum used to “cut” certain
drugs before their intravenous abuse). Amniotic fluid embolism
is a devastating event, often resulting in maternal death
in the peripartum period.
Define pulmonary hypertension. What are the general causes? How common are they?
Normally, pulmonary arterial pressure is approximately oneeighth
that of systemic arterial pressure. Pulmonary hypertension
is defined as a pulmonary arterial blood pressure
greater than or equal to one-fourth systemic arterial blood
pressure. Pulmonary hypertension can be a primary disorder
or a disorder secondary to an underlying condition. Primary
pulmonary hypertension is less common than secondary forms
and is typically sporadic, though familial forms exist.
What is BMPR2 and what does it do? How does it lead to pulmonary hypertension?
In some cases of primary pulmonary hypertension, the
pathogenesis involves a mutation in the gene encoding bone
morphogenetic protein receptor type 2 (BMPR2), a cell
surface protein (in the TGF-β superfamily) that binds many cytokines (including TGF-β, BMP, activin, and inhibin). In
vascular smooth muscle cells of the tunica media, normal
BMPR2 signaling decreases proliferation and increases apoptosis.
An inactivating mutation of the BMPR2 gene, thus,
results in smooth muscle proliferation. Such a mutation is
present in approximately one-half of patients with familial primary
pulmonary hypertension and approximately one-fourth
of patients with sporadic primary pulmonary hypertension.
What occurs in secondary pulmonary hypertension? What are some causes?
In secondary pulmonary hypertension, endothelial cell
dysfunction results from increased shear and mechanical
force, due to increased flow and/or increased pressure, or from
biochemical injury (eg, due to effects of fibrin in the setting of
thromboembolism). Subsequent to endothelial injury, reduction
in prostacyclin and NO leads to pulmonary vasoconstriction,
platelet adhesion, and platelet activation, while various
growth factors and cytokines induce migration and replication
of vascular smooth muscle cells. Many conditions cause
increased pulmonary blood flow, increased pulmonary vascular
resistance, or increased left heart resistance to blood flow
and result in secondary pulmonary hypertension (Table 26.2).
Chronic obstructive lung disease Congenital or acquired heart disease Recurrent pulmonary emboli Autoimmune disorders Obstructive sleep apnea syndromes
What is the morphology of pulmonary hypertension in large, medium, and small arteries?
The morphology of pulmonary hypertension—primary
or secondary—is manifest throughout the pulmonary arterial
tree. Main elastic arteries develop atheromata; medium-sized
arteries develop hyperplasia of the tunica intima and the tunica
media, resulting in thickening of the arterial wall and luminal
stenosis (Fig. 26.5); small arteries and arterioles develop
medial hypertrophy with reduplication of elastic membranes.
How does primary pulmonary hypertension present? In whom does it normally present? How does secondary pulmonary hypertension present?
Clinically, primary pulmonary hypertension affects
young (20- to 40-year old) patients, more commonly women, and presents with fatigue, syncope (especially on exertion),
dyspnea on exertion, and chest pain. Eventually, patients
develop severe respiratory insufficiency and cyanosis, with
death within 2-5 years in more than three quarters of cases.
The clinical scenario in secondary pulmonary hypertension
varies by the underlying disease, though respiratory insufficiency
and right heart failure eventually develop.
Describe Goodpastures syndrome? What is it like epidemiologically? Pathogenitically? Grossly? Microscopically?
Goodpasture syndrome is an autoimmune disease characterized
by the simultaneous development of proliferative
glomerulonephritis (typically crescentic) and necrotizing,
hemorrhagic interstitial pneumonitis. Epidemiologically, it
is associated with certain HLA subtypes and shows a male
predominance; presentation is typically in the teens or twenties.
Pathogenetically, IgG autoantibodies are directed against an
epitope on the α3 chain of collagen IV. Collagen IV is nonfibrillar
and is a key component of basement membranes. The
autoantibody-induced basement membrane damage results in
clinically significant glomerular and pulmonary injury. With
respect to gross pulmonary disease, lungs are heavy, consolidated,
and discolored red-brown. Microscopically, the Goodpasture
syndrome lung shows focal alveolar wall necrosis with
intra-alveolar acute hemorrhage and alveolar septal fibrotic
thickening (Fig. 26.6).
