Hemodynamics Disorders

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Hemodynamics Disorders

• Tutorial activities

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Clinical Case

• A 25-year-old IV drug abuser presents with high
  fever, chills, and rigors. On examination, he is
  found to have a murmur in the tricuspid valve
  area. His face and extremities look flushed, and
  his blood pressure is 90/60.
• Laboratory evaluation reveals an elevated
  leukocyte count with polymorphonuclear
  leukocytosis. Blood cultures grow gram-negative
  bacteria.
• He is treated with intravenous antibiotics. His
  blood pressure continues to fall, and urinary
  output declines to 100 mL/24 hr. Terminally, he
  develops a bleeding diathesis from vein puncture
  sites and mucosal surfaces.
• He dies 3 days later.

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Clinical Case

• 1.What do the fever and leukocytosis indicate?
• 2. What may be the reason for the tricuspid
• murmur?
• 3. What is the basis of thrombus formation
  (vegetations) on the endocardial surface? What
  complications may arise from such vegetations?
• 4. What is the pathophysiology of the low blood
  pressure, oliguria, and renal failure in this
  case?
• 5. What are some of the mechanisms involved in
  the pathogenesis of septic shock?
• 6. What is the pathophysiology of his bleeding?

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Gross Heart, view of the tricuspid valve from
the right atrial
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What might be the consequences of infective
endocarditis with formation of vegetations on the
right side of the heart?

• Embolism to the lung, causing infarction.
  Because the vegetations are infected, the
  necrotic areas can be infected, leading to
  formation of abscesses. Spread to the bloodstream
  may cause septicemia

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Gross outer cutsufaces Kidney, renal tubular
necrosis due to shock
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Why did this patient develop shock?

• This patient had infective endocarditis with
  gram-negative septicemia. The shock resulted from
  release from the bacteria of endotoxins that
  triggered the release of inflammatory mediators
  such as IL-1 and tumor necrosis factor (TNF)

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How did this patient develop shock?

• TNF plays an important role in the development
  of septic shock by promoting the release of IL-1,
  IL-6, IL-8, and nitric oxide, thus initiating a
  cytokine cascade. These mediators, in low to
  moderate quantities, may lead to local
  inflammation and systemic effects, such as fever.
  When present in higher quantities, however, they
  promote the development of shock by causing
  systemic vasodilation, impaired myocardial
  contractility, and widespread endothelial injury,
  which may lead to DIC.

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High power Kidney acute tubular necrosis due to
shock
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What are the major morphologic changes in
multiple organ failure in a patient who dies of
shock?

• Kidneys Acute tubular necrosis.
• Brain Laminar cortical necrosis.
• Lungs Shock lung (diffuse alveolar damage) with
  hyaline membranes (seen mainly in septic shock).
  
• Heart Foci of necrosis, hemorrhage, contraction
  band necrosis.
• GI Hemorrhages.
• Liver Central hemorrhagic necrosis, fatty
  change.

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What is the pathophysiology of acute renal
failure in septic shock?

• Distributive effect Systemic vasodilation leads
  to peripheral pooling of blood and consequent
  reduction in visceral blood flow, including renal
  perfusion.

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Gross coronal section Brain, cortical laminar
necrosis
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How does this picture differ from a
thrombotic/embolic infarct?

• A thrombotic/embolic infarct in the brain is a
  localized lesion present in the area supplied by
  the occluded vessel. In contrast, laminar
  cortical necrosis is due to global hypoxic change
  as in shock, and hence affects a large part of
  the cortical ribbon.

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Gross Heart, aortic valve, infective endocarditis
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What might happen if the infected vegetation
breaks loose from the valve and lodges in a
distant organ?

• Infarction and abscess formation through the
  systemic circulation

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Medium powerHeart, mitral valve,infective
endocarditis
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Could this person develop a cerebral
infarct? What would be the appearance of such an
infarct of the brain? This patient could
develop a cerebral infarct from embolization. The
infarct would be an area of liquefactive necrosis
along with an acute inflammatory response to the
bacteria in the embolus, resulting in brain
abscess formation.
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How is fibrin formed? What are the
categories of coagulant proteins?

• Fibrin is derived from its precursor, fibrinogen,
  a proenzyme. This is one of three types of
  coagulant proteins. The other two are enzymes
  (eg, active coagulation factors) and cofactors
  (eg, factors V and VIII and tissue factor). The
  latter are also called reaction accelerators.

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What complications may arise from this lesion,
infective endocarditis?

• Infected vegetations on the mitral valve may
  embolize systemically and cause infarcts,
  abscesses, or septicemia. In addition, the mitral
  valve, chordae tendineae, or papillary muscles
  may rupture, causing ventricular failure.

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High power Heart, mitral valve, nonbacterial
thrombotic endocarditis
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Medium power Adrenal cortex, disseminated
intravascular coagulation (DIC)
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What are the most common causes of DIC?

• The two most common causes are complications of
  pregnancy (50) and widespread carcinomatosis
  (33). The other major causes include sepsis and
  major trauma.

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What is the spectrum of the clinical course of
DIC?

• The clinical presentation and course of DIC can
  be quite variable, depending on the cause and the
  extent of individual organs involved. Acute DIC,
  dominated by a bleeding diathesis, is associated
  with obstetric complications, septic shock, or
  major trauma. Chronic DIC, dominated by
  thrombotic complications, is associated with
  carcinomatosis.

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What are the common morphologic changes seen in
DIC?

• Microthrombi in many organs - brain, heart,
  lungs, kidney microinfarcts in kidney, brain,
  etc hyaline membranes in lungs adrenal
  hemorrhage in meningococcemia (Waterhouse-Frideric
  hsen syndrome) necrosis of the pituitary gland
  (Sheehan syndrome) fragmented red cells and
  thrombocytopenia on the blood smear

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Diagram Pathogenesis of disseminated
intravascular coagulation -
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What are the two major triggers of DIC?

• Release of tissue factor and endothelial injury.

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What are some of the common sources of tissue
factor that can trigger DIC?

• Major trauma to tissues the placenta in
  obstetric complications mucus released by
  adenocarcinomas granules of leukemic cells in
  acute promyelocytic leukemia bacterial
  endotoxins stimulate release of tissue factor
  from monocytes interleukin-1 and tumor necrosis
  factor stimulate expression of tissue factor on
  endothelial cell surfaces.

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What are some of the common triggers of
endothelial injury in DIC?

• Microorganisms (eg, meningococci, rickettsiae)
  temperature extremes (eg, heat stroke, burns)
  antigen-antibody complexes (eg, systemic lupus
  erythematosus)

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What is the mechanism of DIC in sepsis?

• Bacterial endotoxins promote increased synthesis
  and release of tissue factor from monocytes.
  Activated monocytes also release IL-1 and TNF,
  which increase the expression of tissue factor on
  endothelial cells while decreasing the expression
  of thrombomodulin on endothelial cells. Increased
  tissue factor activates the clotting system.
  Lowered thrombomodulin levels decrease protein C
  activation. Thus, there is simultaneous
  activation of the clotting system and inhibition
  of coagulation control, leading to the formation
  of widespread microthrombi.

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What is the pathophysiology of bleeding in
DIC?

• Bleeding in DIC occurs as a result of the
  consumption of coagulation factors during the
  formation of widespread microthrombi. Widespread
  activation of the fibrinolytic system further
  aggravates bleeding. Plasmin cleaves not only
  fibrin, but also factors V and VIII. In
  addition, fibrinolysis leads to the formation of
  fibrin degradation products, which inhibit
  thrombin, platelet aggregation, and fibrin
  polymerization