Download infarcts

Hemostasis and Thrombosis
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We are not composed of static
pipes that transmit blood, so we
have to understand how the
normal vessel constituents
interact with blood normally!!!!
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Hemostasis is natural process
that maintains blood fluidity while
also controlling vascular injury
repair producing a local
hemostatic plug
PLUMBER’S TOOL
Hemostasis
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Integrity of small blood
vessels
Adequate numbers of
platelets
Normal amounts of
coagulation factors
Normal amounts of
coagulation inhibitors
Adequate amounts of
calcium ions in the blood
Role of endothelium in hemostasis
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Antiplatelet properties
• physical barrier
• Prostacyclin synthesis
• Nitric oxide synthesis
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Anticoagulant properties
• Heparin-like molecules (+antithrombin III inactivate thrombin)
• Thrombomodulin (+thrombin activates Protein C that digests factors
V and VII)
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Fibrinolytic properties
• Synthesis of t-PA
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Pro thrombotic properties
• Synthesis of von Willebrand factor vWF
• Cytokine (Il-1, TNF) stimulation causes release of tissue factor which
in turn activates extrinsic clotting factors
• Synthesis of plasminogen activator inhibitors (PAIs)
Role of platelets in hemostasis:
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Note: Platelets contain 2 types of storage granules:
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Alpha granules store fibrinogen, PDGF, coagulation factors V and VIII.
Dense or delta granules contain ADP, ATP, ionized calcium, histamine,
serotonin, and epinephrine.
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Platelet adhesion: reaction between
platelet surface receptors, vWF,
and collagen
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Platelet secretion: release of granule secretory products that
promote platelet-plug formation
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Platelet aggregation: ADP and thromboxane promote primary
hemostasis. Platelet contraction and fibrin formation lead to
secondary hemostatic plug
Role of coagulation cascade
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Coagulation factor activation occurs on
phospholipid surfaces derived from endothelial
cell injury. This helps to localize the reaction.
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Extrinsic vs. Intrinsic coagulation distinctions are
not clear in vivo.
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Inhibition of coagulation activation is extremely
important and highly dependent on endothelial
integrity.
Sequence of events:
• Initial injury
• Arteriolar vasoconstriction
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Neurogenic reflexes
Local endothelin release (endothelium)
• Exposure of subendothelial matrix (collagen) and platelet
activation (primary hemostasis)
• Tissue factor release (phospholipids) stimulates the
coagulation cascade with net fibrin deposition (secondary
hemostasis)
• Fibrin-platelet plug is formed. Plasmin activation helps
limit plug extension
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
Thrombosis
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Inappropriate activation of the hemostatic process in uninjuried
vasculature or formation of thrombus in the setting of relatively
minimal vascular injury
 Virchow's Triad –predisposing factors
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
Factors predisposing to thrombosis
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Hypercoagulability
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Any alteration of the coagulation pathways that predispose
to thrombosis
• Primary (genetic) Factor V and prothrombin gene
mutations most frequent
• Factor V becomes resistant to protein C inactivation
• Prothrombin levels elevated
• Secondary (acquired)
• Bed rest – immobilization, obesity, cancer, atrial fibrillation,
myocardial infarction, tissue damage (surgery, burns)
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Abnormalities of blood flow
– turbulence
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Endothelial injury
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Local areas of stasis
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Disrupt laminar flow
• Moves platelets from center of
flow to the vessel wall
• Prevent dilution of activated
clotting factors by flowing blood
• Slow down the inflow of clotting
factor inhibitors
• Promotes endothelial cell
activation
Thrombus morphology
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Arterial thrombus:
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Begin at points of injury or areas of turbulence.
Extend in a retrograde fashion
Mural thrombi form in heart or large vessels
Lines of Zahn are indicative of arterial thrombi (adherent
masses of blood that demonstrate areas of pale alternating
with areas of red)
• Arterial thrombi may or may not be occlusive
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Venous thrombus:
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Begin in areas of stasis
Extend in a antegrade fashion
Are almost always occlusive
Contain lots of RBC’s
Long - forming a cast of vein with markings on them from
venous valves
Venous Thrombi: Clinical
Venous trombus
Arterial thrombus
Arterial Thrombi Morphology
Arterial trombus
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
Cardiac thrombi
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Thrombi may form in any chamber of the heart
on the valve cusps
 More common in the atrial appendadages,
especclially of the right atrium, and on mitral and
aortic valvescalled vegetations which may be
seen in infective endocarditis and non –
bacterial endocarditis
 Are mural (non – oclusive) as are the mural
thrombi encountered in the aorta in
atherosclerosis and in aneurysmal dilatations
Fate of a thrombus (venous or arterial)
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Propagation: continued growth
may obstruct critical vessel.
 Embolization: dislodgement of
thrombus or parts of it may
cause obstruction downstream.
 Dissolution: fibrinolysis may
dissolve clot.
 Organization: thrombus
induced injury leads to
inflammation and fibrosis. Recanalization may re-establish
some vascular flow.
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Venous thrombi fates
Effects of thrombosis
 Ischemia
 Congestion
 Heart
valve disease
 DIC
 Embolism
Disseminated Intravascular
Coagulation
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Sudden onset of fibrin thrombi in the microcirculation with
consumption of coagulation factors and formation of fibrin
degradation products
 A potential complication of any disease state/process
associated with the widespread activation of thrombin
 Not usually visible “grossly”, readily apparent microscopically
and can cause diffuse circulatory insufficiency, particularly in
the brain, lungs, heart, and kidneys
 development of the multiple thrombi rapid concurrent
consumption of platelets and coagulation proteins (synonym
consumption coagulopathy);
 at the same time, fibrinolytic mechanisms are activated
bleeding disorder.
DIC
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Obstetrical complications
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Infection
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trauma, burn, surgery)
Vasculitis and vascular malformations
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promielocytic leucemia
Tissue injuryies
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pancreatic, prostate, lung, stomach carcinoma
Sanguine disorders
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gram negative, meningococc, aspergillosis, malaria
Neoplasm
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abruptio placentae, ritention of death fetus, septic abortion, amniotic
liquid embolism
hemangiom, anevrism)
Varies
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intravascular hemolisis, hepatopaties
Pathophysiology of disseminated intravascular
coagulation.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
DIC
Embolism
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Embolism is the process of partial or
complete obstruction of some part of the
cardiovascular system by any mass carried
in the circulation.
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The transported intravascular mass detached from its
site of origin is called embolus ( solid, liquid, or gaseous
mass).
90% of all emboli are derived from a thrombus.
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Types of emboli
A. Depending upon the matter in the emboli:
 Solid – detached thorombi, atheromatous materal,
tissue fragments, parasites, foreign bodies
 Liquid – fat globules, amniotic fluid, bone marrow
 Gaseous- air, other gases
B. Depending upon wheter infected or not
 Bland, when sterile
 Septic, when infected
C. Depending upon source of emboli
 Cardiac emboli
 Arterial emboli
 Venous emboli
 Lymphatic emboli
D. Depending upon the flow of blood
 Paradoxical embolism : In patients with persistent
oval hole, embolism from the venous system can pass
from the right to the left side of the heart and reach the
systemic circulation.
 Retrograde embolism: circulating emboli in the
reverse sense of blood flow - e.g. metastatic deposits
in the spine from prostate carcinoma (the spread ooccurs
by retrograde embolism through intraspinal which carry tumour
emboli from large thoracic and abdominal veins veins due to
increased pressure in body cavities).
Direct or ortograde embolism: emboli originating from the
left heart and systemic circulation reach to cerebral, renal or
splenic arteries; embolism from leg veins reach the lung
Paradoxical emboli
• arise in venous
system and pass
through a hole in
interventricular
septum of the heart
and end up in the
arterial system
(possible stroke).
Sources of artherial and venous emboli
Concequences of embolism
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Obstruction of a vessel ->ischemia
(with the instalation of stroke, gangrene or swelling
of the brain, e.g)
Infarction of the organ or its affected part –
ischaemic necrsis in the lower limbs, spleen, brain,
intestine
septicemia (septic emboli)
Sudden death by massive pulmonary embolism,
coronary embolism, embolism in the middle cerebral
artery
Arteritis or mycotic aneurysm formation from
bacterial endocarditis
Myocardial infarction
 Pulmonary
Thromboembolism
• 10% of hospital patients die from this (50,000/yr).
• 95% originate in the deep veins of the legs above
knee.
• Saddle embolus is one that lodges at the
common iliac bifurcation.
• Most are asymptomatic due to small size.
• With greater than 60% of pulmonary arterial
system blocked patients develop sudden cardiac
death, cor pulmonale, or shock.
• Multiple emboli may result in pulmonary
hypertension.
PULMONARY EMBOLISM
Concequences of pulmonary embolism
Thromboembolus in a
large pulmonary artery
Hhromboembolus small
peripheral artery
Systemic Thromboembolism
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Arterial emboli
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80% arise in the heart (mural thrombi).
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Major lodgment sites include lower extremities
(75%) and brain (10%). Intestines, kidneys, and
spleen are also targets.
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Consequences dependent on size of emboli,
caliber of vessel, collateral circulation, and tissue
sensitivity to ischemia
Bone marrow embolus in the pulmonary circulation
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
Other types of emboli
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Fat Emboli
• Major source is long bone fracture.
• They develop in 90% of severe fractures but most are asymptomatic.
• In cases of significant emboli development consequences include
pulmonary insufficiency, stroke, anemia, and thrombocytopenia. (10%
fatal)
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Air Emboli
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Causes include chest wall injury or obstetric procedures.
100 cc or more of air is clinically significant.
Bends results from decompression problems.
Caisson disease is chronic bends.
Amniotic Fluid Emboli
• 1/50,000 deliveries
• Mortality rate > 80%
• Causes include placental tears and uterine vein rupture.
AIR EMBOLISM - symptoms
AIR EMBOLISM
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Septic embolism
• Causes include IV drug use, right-sided infective
endocarditis, and septic thrombophlebitis.
• symptoms and signs of pneumonia or sepsis.
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Foreign body embolism
• caused by introduction of particulate matter into the
pulmonary arterial system - IV injection of inorganic
substances: talc by heroin users or elemental mercury
by patients with mental disorders.
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Tumor embolism
• complication of malignancy (usually adenocarcinoma)
• neoplastic cells from an organ enter the systemic
venous and pulmonary arterial system, where they
lodge, proliferate, and obstruct flow.
Fatty emboli
Metastatic embolus
Amniotic Fluid Emboli
Atheroemboli
(Kidney)
Septic embolus
Infarction
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Def.: ischemic necrosis of tissue distal to an area of arterial
occlusion or in an area of obstructed venous outflow
Most result from atherosclerosis - the major cause of MI and
stroke.
Commonly seen in kidney, spleen, lung, intestine, heart and
brain
Usually located beneath the tunica of the organ.
Classified:
• on the basis of their colour (reflecting the amount of
hemorrhage):
 red (hemorrhagic)
 white (anemic)
• presence or absence of microbial infection:
 septic
 bland
 Influencing
Factors
• Nature of vascular supply: alternative blood supply is
most important (lung and liver)
• Rate of development: collateral development limits
infarction.
• Tissue vulnerability: neurons (3 min), heart (25 min),
connective tissue (hours)
• Blood oxygen content: patients with anemia or those
cyanotic are more susceptible.
Morphology
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Red (hemorrhagic) infarcts occur :
• with venous occlusions (ovarian torsion);
• in loose tissues (lung), which allow blood to collect in the
infarcted zone
• in tissues with dual circulations (e.g., lung and small
intestine), permitting flow of blood from the unobstructed
vessel into the necrotic zone
• in tissues that were previously congested because of
sluggish venous outflow
• when flow is re-established to a site of previous arterial
occlusion and necrosis (e.g., following fragmentation of
an occlusive embolus or angioplasty of a thrombotic
lesion)
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White (anemic) infarcts occur with arterial occlusions in solid
organs with end-arterial circulation (heart, spleen, and kidney),
where the solidity of the tissue limits the amount of hemorrhage
 Shape
of infarct
• Wedge-shape: infarct of liver, spleen, kidney,
lung;
• Map-like shape: myocardial infarct;
• Segmental shape: intestinal infarct.
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At early stage, all infarcts are poorly defined. The
margins of both types of infarcts tend to become better
defined with time by a narrow rim of hyperemia and/or
hemorrhage attributable to inflammation at the edge of
infarct
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Histopathology
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dominant histologic characteristic:
• Coagulative necrosis: liver, spleen, kidney, myocardium,
lung
• Liquefactive necrosis: brain, pancreas
The infarct is a kind of tissue necrosis among which
pyknosis, karyorrhexis and karyolysis can be seen.
The outline of original tissue can be discerned despite
that the cells are dead.
Anemic infarct contains few RBC; while hemorrhagic infarct
has engorgement and hemorrhage;
The pathological changes secondary to infarct: hyperemia,
hemorrhage, inflammation, organization.
Most infarcts are ultimately replaced by scar tissue
Infarction
Red (Hemorrhagic)
Anemic (White)
Pulmonary infarct
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Embolization to the small
vessels in lung may cause
ischemic necrosis of tissue or
infarct
Heart infarction
Infarction
1 to 2 days in duration
contraction
band necrosis
Infarction
is about 3 to 4 days old
Infarction
of 1 to 2 weeks in age
Old infarction
Aneurism of ventricle
Rupture
of the myocardium
Intestinal infarction
Arterial thrombosis/
embolism
Venous thrombosis
Nonoclussive ischemia/
Miscellaneous
-radiation injury
-volvulus
-stricture
-herniation
Liver Infarct
Kidney infarct
Myocardial Infarction
Acute Myocardial Infarction
 interruption of blood supply to a part of the
heart, causing necrosis of heart muscle
due to ischemia
Mechanism
 Subendocardial (prologend ischemia
caused by partial occlusion of a coronary)
 Transmural (complete occlusion of a major
coronary)
Common localisations and the regions
involved in myocardial infarction
Complications of myocardial
infarction
 Arrrithmias
 Congestive
heart failure
 Cardiogenic shock
 Mural thrombosis and thrmboembolism
 Rupture
 Cardiac aneurysm
 Pericarditis
 Postmyocardial infarction syndrome
Shock
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Shock = Cardiovascular Collapse
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Results from systemic hypoperfusion due to either a reduction in
blood volume or cardiac output.
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Types of Shock
• Cardiogenic: MI, arrhythmia, tamponade, outflow
obstruction
• Hypovolemic: traumatic hemorrhage, severe burns, disease
induced hemorrhage.
• Neurogenic: Cord transection (peripheral pooling)
• Anaphylactic: IgE mediated vasodilation and edema
• Septic: Systemic infection primarily gram-negative
(endotoxic). Cytokine mediated vasodilation,
myocardial injury, and DIC.
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Stages of Shock
• Initial non progressive stage: tachycardia,
vasoconstriction, renal conservation of water.
• Progressive stage: lactic acidosis, vasodilation, hypoxia,
organ failure.
• Irreversible stage: Lysosome release, ischemic bowel
syndrome, acute tubular necrosis, death.
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Clinical Course
• Hypovolemic/Cardiogenic: hypotension, weak rapid
pulse, tachypnea, cool clammy cyanotic skin.
• Septic shock: warm red skin.
80% with hypovolemic shock survive.
80% with cardiogenic or endotoxic shock die.
Model of septic shock