Fluid & Hemodynamic disorders 2 Flashcards
Fibrin
A polymerized fibrinogen
Forms mesh network of thin filaments biding blood cells to form thrombus or hemostatic plug
Thrombosis
Transformation of a fluid into a solid
Clotting of whole blood into an aggregate of blood cells and fibrin
Thrombus pathogenesis
Thrombi from only in living organisms
End products of the coagulation sequence
Normally activated to prevent blood loss from disrupted vessels
If coagulation sequence activated in intact vessels pathological thromboses develop
what will promote thrombosis and what will counteract it
Clotting factors and platelets promote thrombosis
Endothelial cells and plasmin counter act it
Under normal conditions, clotting and anti-clotting are in balance.
Intravascluar coagulation is the result of interaction between:
- Coagulation proteins
- Endothelial cells
- platelets
Coagulation proteins
Cascade sequence of activation culminates in thrombin
Thrombin is catalyst, promoting polymerization of fibrinogen into fibrin
Meshwork of fibrin is the frame work for the clot which includes blood cells and proteins
Thrombin promotes
Polymerization of fibrinogen into fibrin
Endothelial cells
Normal resting endothelial cells have antihromboti function, but if activated, will initiate coagulation
Can initiate thrombosis
E.g. IL-1 and TNF
What will activate Endothelial cells to coagulate?
Inflammation or trauma
Cytokines also activate endothelial cells
Patelets
Neutralize heparin and other anticoagulation factors
Secrete thromboxane
Coagulation stimulation
What will degrade thrombi
Thrombolytic chemicals like plasmin
Pathologic thrombus formation
Virchow’s Triad (predisposing factors)
- Endothelial cell injury
- Hemodynamic changes
- Hypercoagulability of whole blood
Virchow’s triad 1:
Endothelial cell injury
Intact endothelium has anticoagulant properties
Under influence of inflammatory mediators, endothelium loses antithrombotic properties
Virchow’s Triad 2
Hemodynamic change
- Disturb noral laminar flow resulting in turbulence and margination
- slow blood flow results in sedimantation and blood eddies
- small thrombi no dissolved by thrombolytic substance tend to persist or even grow in sluggish blood stream
Virchow’s Triad 3
Hypercoagulability
- blood is hypercoagulable in severe burn victims probably due to severe fluid loss and hemoconcentration
- also in cancer, chronic cardiac failure and pregnancy
Intramural thrombi
mural endocardium - attached to wall of heart chambers and commonly found overlying myocardial infarction
Thrombi attached to wall of heart chambers
Intramural thrombi
Fibrinous growths in debilitated persons, mimics endocarditis
Valvular thrombi
AKA non-bacterial (marantic) or sterile thrombotic endocarditis
Attached to arterial wall
Arterial thrombi cover ulcerated atheromas in aorta or coronary arteries
Arterial thrombi cuases
Atherosclerosis/aneurysms
Thrombi attached to veins
Venous thrombi, common in varicose veins
Chronic may lead to organized granulation tissue and inflammation (thrombophlebitis)
Thrombi in arterioles, capillaries, venules
Microvascular thrombi
Typical of Disseminated Intravascular Coagulation (DIC)
Thrombi in small vessels are red
Composed of tightly intermixed RBC and fibrin
Red (conglutination) thrombi
Distinct layering of cellular elements and fibrin (white line), in large arteries, veins, mural thrombi
Layered (sedimentation) thrombi
What does white lines in Layered thrombi
Lines of Zahn
Why is Red thrombi red?
Because intermixed with RBC
What is kind of thrombi seen in varicose veins?
Venous thrombi
Thrombi mimics endocarditis
Valvular thrombi
Fate of thrombi depends on
Size, location, hemodynamics of vessel
Most small thrombi lysed without consequence
Larger thrombi remain attached to surface of vessel wall or endocardium
Stages of fate of thrombi 1
Attachment initially mediated by adhesion molecules such as fibronectin or fibrin
Eventually thrombus can stimulate ingrowth of inflammatory cells and vessels
Granulation tissue forms firmer anchorage - organization
Stage of thrombi 2
Inflammatory cells of granulation tissue dissolve the thrombus
Granulation tissue replaced by collagenous fibrous tissue
Occlusive thrombi can be recanalized
Can become break off and become emboli
Can block blood vessel leading to infarction
Clinical correlations
Thrombotic occlusions of cardiac and cerebral arteries are a major cause of death in US
Clinical symptoms depend on site, extent of thrombi, rapidity with which they form, duration of thrombosis, widespread nature of disease complications
Thromboi clinical correlations: occlusion of lumen of blood vessel causes
Ischemia
Clinical correlations of thrombi: Sudden thrombotic occlusion of coronary arteries most common cause of
Myocardial infarction
Clinical correlations of Thrombi: Slowly narrowing of lumen of blood vessel and decrease in blood flow results in
Hypoxia and reduced function of affected organ over time (Chronic heart failure)
Thrombus detached and free flowing in blood is called
Embolus
Emboli can become lodged in arteries and lead to
Infarct
Cerebral infarct
Stroke
Thrombus can accelerate the development of
atherosclerosis
Thrombus can become infected and break off
Septic emboli
A freely movable intravascular mass that is carried from one anatomical site to another by blood
Embolus
Plural of embolus
Emboli
Infarct caused by embolus
Emoblism
Thrombi carried by venous or arterial blood
Thromboemboli
fat emboli following bone fracture (femur), amniotic fluid emboli in veins
Liquid emboli
Air injected into veins, air liberated under decreased pressure (caisson disease or decompression sickness)
Gaseous emboli
Cholesterol, tumour cells, bone marrow
Solid particle emboli
All emboli can
occlude blood vessels resulting in decreased blood supply to organ (ischemia)
Only clinically significant emboli
Thromboemboli all others are rare
Where does venous emboli typically lodge and cause
Typically lodge in pulmonary artery and cause pulmonary embolism
Smaller emboli cause pulmonary infarcts - subpleural pain
What does arterial emboli cause
Common cause of ischemia in spleen, kidney, intestines
Usually originate from cardiac mural or valvular thrombi
Can also originate from aorta
Characteristics of arterial emboli
Mechanically fragmented inside vessels because arterial blood flows fast and disrupts them
Therefore tend to lodge in small and medium-sized arteries
Greatest risk in cerebral circulations
What does emboli lodge in middle cerebral artery cause
infarcts of basal ganglia, associated with high mortality and neurological defects
What kind of emboli cause infarcts with sharp subcostal pain?
splenic emboli
What kind of emboli causes infarcts with subpleural pain
smaller venous emboli cause pulmonary infarcts
Painful and associated with hematuria
Renal infarcts
Medical emergency, can cause gangrene of intestines
Intestinal infarct
infarcts of basal ganglia
emboli in middle cerebral artery, associated with high mortality and neurological defects
Intestinal infarct
Medical emergency, can cause gangrene of intestines
Renal infarcts
Painful and associated with hematuria
Splenic emboli
cause sharp subcostal pain
Infarction
sudden insufficiency of blood supply resulting in an area of necrosis
most are caused by thrombi or thromboemboli
May be classified by origin as arterial or venous
Can be further classified by appearance as white or red
White or pale infarcts
typical of solid organs
E.g. heart, kidney, spleen
Ischemic necrosis paler than surrounding tissue
Blood may infiltrate from collateral arteries resulting in mottled appearance
Red infarcts
Typical of venous infarction
E.g. particulary of intestines or testes
Circulation can be interrupted by twisting organ
E.g. torsion of testes
Fate of infarcts depends on
Anatomic site
Circulatory status
Capacity for repair
Ischemic necrosis of Post mitotic cells
ischemic necrosis of post-mitotic cells (e.g. heart) can not be repaired -only replaced with fibrous tissue (scarring).
Necrotic brain cells
can not be repaired, but liquefactive necrotic tissue resorbed. Leaves clear fluid filled cyst
Mitotic tissues and facultative (occurring optionally in response of circumstances, but not of nature) mitotic tissue
heal with relatively few defects - e.g. liver, however large infarcts may be impossible to regenerate completely - leaves scarring and loss of function
