Hemodynamic Disorders

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Hemodynamic Disorders

• Tutorial Activities
• Dr Awatif Jamal

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Grosscut surface Lung acute pulmonary congestion
and edema
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Low power Lung, acute passive congestion and
edema
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Gross, cut surface Lung, chronic passive
congestion
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Medium power Lung, chronic passive congestion
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Gross, cut surface Liver, chronic passive
congestion with centrilobular necrosis
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Medium power Liver, chronic passive congestion
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Medium power Liver, chronic passive congestion
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Gross, cut surface Spleen, chronic passive
congestion (case of heart failure)
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Lymphedema, filaria infection Clinical
presentation
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Breast, lymphedema secondary to breast carcinoma
Clinical presentation
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Gross Heart and lungs, pulmonary thromboembolus -
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Gross Pulmonary artery, pulmonary thromboembolus -
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Deep vein thrombosis - Clinical presentation
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Gross, cross section Veins, iliac, with thrombi
(death caused by massive pulmonary embolus)
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High power Vein with organizing and recanalizing
thrombus
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Gross, cross section Coronary artery, right, with
thrombus
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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.
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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.

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Clinical Case

• 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.

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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?
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Heart, coronary artery angiography Radiograph
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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.

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• 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.
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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.

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low-power micrograph Heart, coronary artery -
Angiography radiograph
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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.

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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.

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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.

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Gross, cross section Coronary artery, right, with
thrombus
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Low power Heart, coronary artery thrombosis
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What is the thrombus made of?

• Fibrin, platelets, and red cells.

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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.

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What are the various fates of thrombi?

• Propagation, embolism, dissolution, and
  organization with recanalization.

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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.

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Heart, myocardial infarct acute vs healed -
Gross, cross section

• Healed infarct fibrosis

• Acute infarct coagulative necrosis and surrounded
  by hyperemia

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Gross, coronal section Brain, cerebral infarct
acute
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What are the major similarities between a
myocardial and a cerebral infarct?

• 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.

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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.

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What is the mechanism of formation of hemorrhagic
infarcts in brain?

• 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.

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Gross, cut surface Liver, chronic passive venous
congestion
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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).

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Gross Lung, chronic passive venous congestion
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What is the brown pigment that is derived from
hemoglobin?

• Hemosiderin.

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Medium powerLung, acute pulmonary congestion and
edema
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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).

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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.
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High power Lung, chronic passive venous
congestion
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Are the alveolar septa normal in thickness?

• They are thickened, due to edema and reactive
  fibrosis.

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What effect would such a histologic picture have
on gaseous exchange in the lung?

• It would be markedly impaired

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What might the symptoms be?

• Dyspnea, orthopnea, paroxysmal nocturnal dyspnea,
  and cough

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Gross, cut surface Lung, pulmonary infarct
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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.

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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).

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What conditions predispose to venous thrombosis?

• Venous stasis caused by prolonged immobilization
  (eg, in hospitalized patients after surgery) or
  by congestive heart failure.

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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.

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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.

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Medium power Lung, infarct
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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.

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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).

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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.

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High power Lung, infarct
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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.

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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.

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In what respects does amniotic fluid embolism
significantly differ from a typical venous
pulmonary thromboembolism?

• 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.