Transcript Gross, cut surface Lung, acute pulmonary congestion and edema

Hemodynamic Disorders
Tutorial Activities
Dr: Awatif Jamal
Gross
cut surface
Lung acute
pulmonary
congestion
and edema
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Low power
Lung, acute
passive
congestion
and edema
Gross, cut
surface
Lung, chronic
passive
congestion –
Medium power
Lung, chronic
passive
congestion
Gross, cut
surface Liver,
chronic
passive
congestion
with
centrilobular
necrosis –
Medium
power
Liver,
chronic
passive
congestion
Medium
power
Liver,
chronic
passive
congestion
Gross, cut
surface
Spleen,
chronic
passive
congestion
(case of
heart
failure)
Lymphedema,
filaria
infection –
Clinical
presentation
Breast,
lymphedema
secondary to
breast
carcinoma –
Clinical
presentation
Gross
Heart and
lungs,
pulmonary
thromboem
bolus -
Gross
Pulmonary
artery,
pulmonary
thromboemb
olus -
Deep vein
thrombosis Clinical
presentation
Gross, cross
section Veins,
iliac, with
thrombi (death
caused by
massive
pulmonary
embolus) –
High
power
Vein with
organizing
and
recanalizin
g thrombus
Gross, cross
section
Coronary
artery, right,
with
thrombus
Clinical Case
A 65-year-old man presented to the emergency room
with a recent (4-hour) history of severe chest pain
radiating to his left arm. He was suspected to have
had a "heart attack." Coronary angiography revealed a
complete occlusion of the left anterior descending
branch about 2 cm from its origin.
He was given a therapeutic dose of recombinant
human tissue plasminogen activator (t-PA). This
treatment restored coronary artery blood flow, and his
chest pain improved. Simultaneously, he was started
on one tablet of aspirin per day.
Clinical Case


Seven days later, he noted swelling of both
legs and feet and was found to have pitting
edema of the legs; his liver was somewhat
enlarged; and his neck veins (jugular)
appeared full.
He was given diuretics and asked to consume a
salt-restricted diet. Because of considerable
weakness, he remained in bed most of the time.
Clinical Case



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A few days later, he developed sudden pain in the
lower right part of his chest, which was aggravated
by taking a deep breath.
Physical examination revealed that his left leg had
developed more swelling than the right.
X-ray of his chest showed a faint shadow in the
peripheral part of the lower lobe of the right lung.
Intravenous heparin was started.
Two days later, he became very breathless and
died suddenly.
Questions
1-What is the basis of thrombosis in the coronary artery?
2- What are the factors that predispose to arterial versus venous
thrombosis?
3-Why was t-PA given? What is the mechanism of action of t-PA?
4-What are the other naturally occurring anticoagulants?
5- Why is aspirin given in such cases? What stage of hemostasis is
affected by aspirin?
4- Why did the patient develop edema initially?
5- What are the factors that predispose to generalized edema?
6- Why did he later develop more edema in one leg? Why are
patients with edema given a salt-free diet?
7- What are the clinical settings in which venous thrombosis of leg
veins occurs? What is the most feared consequence?
Heart,
coronary
artery
angiography
Radiograph
What therapeutic agent can be used to lyse the clots
in coronary vessels?
How do the various natural anticoagulants act?

Thrombolysis can be accomplished by tissue
plasminogen activator (t-PA) or streptokinase;
both cause fibrinolysis by generating plasmin.
Why was aspirin given? What stage
of hemostasis is affected by aspirin?
Aspirin prevents thrombogenesis by
inhibiting platelet aggregation.
This is achieved by inhibition of
cyclooxygenase, thereby preventing
the generation of thromboxane A2.
How do the various natural
anticoagulants act?
There are three natural anticoagulants:
(1) The protein C system generates active protein C that
inactivates cofactors V and VIII. Protein C itself is
activated by thrombin after the latter binds to
thrombomodulin on the endothelium.
(2) Antithrombin is activated by binding to heparin-like
molecules on the endothelium; activated antithrombin
causes proteolysis of active factors IX, X, and XI, and
thrombin.
(3) Plasmin cleaves fibrin. It is derived from its circulating
precursor, plasminogen, by the action of tissue
plasminogen activator, which is synthesized by
endothelial cells.
low-power
micrograph
Heart,
coronary
artery Angiography
& radiograph
What is the difference between a
postmortem clot and a thrombus?


Postmortem clots are not attached to endothelium;
they are gelatinous, rubbery, dark red at the ends
and yellowish elsewhere.
Thrombi are attached to endothelium and are
traversed by pale grey fibrin strands that can be
seen on cut section; they are more firm but fragile.
What stage in the formation of a thrombus is
targeted by the currently used antithrombotic
medications?
The most important stage in thrombogenesis that is inhibited by the
current antithrombotic medications is platelet aggregation.
This crucial step requires binding of platelets by fibrinogen
molecules, which attach to platelets at the GPIIb/IIIa receptor.
Different antithrombotic drugs inhibit platelet aggregation in different
ways. For example, aspirin inhibits synthesis of thromboxane A2.
Newer drugs inhibit ADP-mediated structural alterations in the
GPIIb/IIIa receptor, thus preventing binding of fibrinogen to this
receptor. Drugs that directly bind and inhibit the GPIIb/IIIa receptor
are also available for experimental trials.
What are other causes of arterial
thrombosis?
Arterial thrombosis is caused by injury to the
endothelium. In addition to atherosclerosis,
other causes are vasculitis and trauma.
Gross, cross
section
Coronary
artery, right,
with
thrombus
Low power
Heart,
coronary
artery
thrombosis
What is the thrombus made of?
Fibrin, platelets, and red cells.
What causes arterial thrombosis?
..venous thrombosis?
Arterial thrombosis is caused by endothelial
damage (eg, atherosclerosis or vasculitis);
venous thrombosis is caused by stasis
(sluggishness) of blood flow.
Both types of vessels are affected in
hypercoagulable states such as antithrombin
or protein C deficiency.
What are the various fates of thrombi?
Propagation, embolism, dissolution, and
organization with recanalization.
Which of these fates is clinically most
significant in the arterial circulation vs.
the venous circulation?

The most significant problem with arterial thrombi is
propagation leading to luminal obstruction, resulting in
infarction of the tissue supplied. Important examples
include myocardial and cerebral infarction. In contrast,
the most significant problem with venous thrombi is
the possibility of potentially fatal embolization into the
pulmonary circulation.
Heart, myocardial infarct: acute vs healed Gross, cross section

Healed infarct fibrosis

Acute infarct
coagulative necrosis
and surrounded by
hyperemia
Gross,
coronal
section
Brain,
cerebral
infarct:
acute
What are the major similarities between a
myocardial and a cerebral infarct?
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The major similarity is in the etiology.
Both types of infarcts are commonly caused
by thrombotic occlusion of the arteries
supplying them.
Thrombi usually form on the same underlying
disease process (ie, atherosclerotic arterial
disease).
Also, the early histologic reactions, such as
neutrophilic infiltration and granulation tissue
formation, are common to both.
What are the major differences between a
myocardial and a cerebral infarct?

A myocardial infarct typically features
coagulative necrosis, which heals by fibrosis
and leaves behind a fibrous scar. In contrast,
a cerebral infarct is typically liquefactive
necrosis, in which dead tissue is digested
without being replaced by fibrosis, leaving
behind a cystic, cavitary lesion.
What is the mechanism of formation of
hemorrhagic infarcts in brain?
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
Brain infarcts can be pale or hemorrhagic.
Hemorrhagic infarcts are due to arterial
occlusion followed by reperfusion.
Examples are embolic occlusion followed by
fragmentation of emboli or occlusive
vasospasm that later is relieved.
Gross,
cut
surface
Liver,
chronic
passive
venous
congestion
What caused enlargement of the liver,
edema, and fullness of the neck veins in this
patient?
This patient had ischemic heart disease due
to coronary thrombosis. This led to failure of
the left ventricle and, eventually, of the right
ventricle, giving rise to congestive heart
failure. Because of impaired venous return to
the heart, the neck veins become distended,
the liver becomes enlarged, and fluid collects
in interstitial spaces (edema).
Gross
Lung,
chronic
passive
venous
congestion
What is the brown pigment that is
derived from hemoglobin?

Hemosiderin.
Medium
power
Lung, acute
pulmonary
congestion
and edema
What is the pathogenesis of pulmonary
edema?


Left ventricular failure (eg, caused by a
myocardial infarct) causes pump failure, and
secondarily there is impaired flow of blood
from the lung to the left atrium. This causes
increased hydrostatic pressure in pulmonary
alveolar capillaries and subsequent
transudation of fluid into alveoli.
Pulmonary edema in other cases may also
result from damage to alveolar capillaries (eg,
in adult respiratory distress syndrome).
How does this type of edema differ
from that seen in acute inflammation?
The fluid in pulmonary edema is a
transudate (ie, it is protein poor, has low
specific gravity, and does not contain
inflammatory cells). Edema in
inflammation is an exudate.
High power
Lung, chronic
passive venous
congestion
Are the alveolar septa normal in
thickness?

They are thickened, due to edema and
reactive fibrosis.
What effect would such a histologic picture
have on gaseous exchange in the lung?

It would be markedly impaired
What might the symptoms be?

Dyspnea, orthopnea, paroxysmal nocturnal
dyspnea, and cough
Gross, cut
surface
Lung,
pulmonary
infarct
Did this patient have clinical features
suggestive of pulmonary thromboembolism?

Yes. He had deep vein thrombosis in his left leg,
which most likely was the source of an embolus.
His chest pain that was exaggerated by
breathing suggests pleural inflammation
overlying an infarct in the right lower lobe.
Massive pulmonary thromboembolism was the
probable cause of his death.
Why are some infarcts red and others
pale?

Red infarcts result from hemorrhage into the
necrotic area. This is likely to occur in tissues that
have a loose texture and dual blood supply (eg,
lung); by contrast, pale infarcts occur in compact
tissues and those in which the collaterals do not
readily refill the necrotic area (eg, heart).
What conditions predispose to venous
thrombosis?

Venous stasis caused by prolonged
immobilization (eg, in hospitalized patients
after surgery) or by congestive heart failure.
What is the most common source of clinically
significant pulmonary emboli (ie, thrombi from which
vessels in the leg)?

The vessels are the large, deep veins of the
leg above the knee joint. These include
popliteal veins, femoral veins, and iliac veins.
Thrombi in these vessels often do not
produce local symptoms. In contrast, thrombi
in superficial veins often produce pain,
edema, and varicose ulcers, but usually do
not embolize.
What is the most common symptom
associated with such venous thrombi?

There are no symptoms in about 50% of
cases. Local pain and edema occur in the
remaining cases.
Medium
power Lung,
infarct
What is the most common symptom of
pulmonary embolism?

There are usually no symptoms. Most
pulmonary emboli (60-80%) are clinically
silent because of their small size and
because of the dual blood flow through the
bronchial circulation. With time, these emboli
organize and are incorporated into the vessel
wall.
How and when does pulmonary
thromboembolism cause sudden death?
If more than 60% of the pulmonary circulation
is obstructed by emboli, the patient is at a
high risk of sudden death due to acute right
heart failure (cor pulmonale) or shock
(cardiovascular collapse).
When does pulmonary thromboembolism result
in infarction?

The possibility of developing pulmonary
infarction is higher in a previously diseased
lung, especially in the setting of sluggish
bronchial arterial flow or prior pulmonary
congestion due to left heart failure.
High power
Lung,
infarct
What is the risk of recurrence of
pulmonary thromboembolism?

In general, the patient who has had one
pulmonary embolus is at a higher risk of having
more.
In what respects does fat embolism
significantly differ from a typical venous
pulmonary thromboembolism?

Fat embolism occurs after fractures of long bones,
major soft tissue trauma, or severe burns. Most
patients with fat embolism are asymptomatic, just like
venous thromboembolism. But in those cases (less
than 10%) that are symptomatic, besides pulmonary
insufficiency, patients also develop neurologic
symptoms, skin rashes, and, sometimes, anemia and
thrombocytopenia. Microscopically, the emboli
consist of fat or marrow particles.
In what respects does amniotic fluid embolism
significantly differ from a typical venous
pulmonary thromboembolism?
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Amniotic fluid embolism, in contrast, is a grave
condition, with mortality in excess of 80% due to
respiratory insufficiency, shock, DIC, seizures, and
coma.
This condition is a rare complication of labor (1 in
50,000 deliveries).
Microscopically, pulmonary vessels contain
squamous cells and mucin (contents of amniotic
fluid) derived from fetal skin and intestinal tract.