Transcript Hemodynamics Disorders

Hemodynamics Disorders
Tutorial activities
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.
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?
Gross
Heart,
view of
the
tricuspid
valve from
the right
atrial
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
Gross
outer & cut
sufaces
Kidney,
renal
tubular
necrosis
due to
shock
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)
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.
High power
Kidney
acute
tubular
necrosis
due to
shock
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.
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.
Gross
coronal
section
Brain,
cortical
laminar
necrosis
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.
Gross
Heart, aortic
valve,
infective
endocarditis
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
Medium power
Heart, mitral
valve,infective
endocarditis
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.
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.
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.
High power
Heart, mitral
valve,
nonbacterial
thrombotic
endocarditis
Medium power
Adrenal
cortex,
disseminated
intravascular
coagulation
(DIC)
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.
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.
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 (WaterhouseFriderichsen syndrome); necrosis of the
pituitary gland (Sheehan syndrome);
fragmented red cells and thrombocytopenia on
the blood smear
Diagram
Pathogenesis
of
disseminated
intravascular
coagulation -
What are the two major triggers
of DIC?
• Release of tissue factor and endothelial
injury.
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.
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)
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.
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