Hemodynamic disorders II

Normal homeostasis

• Normal homeostasis is to maintain the blood in fluid state in

blood vessels

• When , endothelial injury – thrombosis formation take place :

1. Vasoconstriction
2. Primary homeostasis-clot formation
3. Secondary homeostasis – clotting pathway activation
4. Fibrinolytic system activation
 Normal homeostasis

• Vascular injury – exposure to the extra cellular matrix (ECM) –

that expose the vonwillibrand factor(vW factor) of ECM –
bind the platelets :
 Platelet adhesion ,shape change
 Secretion
 Aggregation
 Coagulation cascade

• Intrinsic and extrinsic pathways

• Both pathways at the end –thrombin formation
• Thrombin convert the fibrinogen into fibrin
• Use of vitamin k and calcium in the many steps of pathways

• Fibrinolytic pathways :
 tpA and urokinase convert the plasminogen into plasmin
 Plasmin degrade the fibrin into fibrin degradation product
(FDP)
 Properties of endothelium

• Not injured endothelium – antiplatelet, anticoagulant effect

and fibrinolytic effect
• Injured endothelium – procoagulant activity
1. platelet effect – aggregation of platelets after exposure of
vWF
2. procoagulant effect –in response to cytokines ,endothelial
cell synthesize tissue factors – actiation of extrinsic clotting
factors /cascade
3. Antifibrinolytic effect –endothelial cells secret PAIs –inhibit
fibrinolysis and favor thrombosis
 Pathogenesis of Thrombosis

• The primary abnormalities that lead to thrombosis are (the

so-called Virchow triad):

(1)endothelial injury
(2) stasis or turbulent blood flow
(3) hypercoagulability of the blood
 Causes of thrombosis – 1. endothelial injury

• Endothelial injury – physical loss of endothelial

• Endothelial dysfunction -
 Hypertension
 Bacterial toxin
 Radiation
 Hyper cholesterol
 Smoking
 Causes of thrombosis – blood flow alteration

• Stasis and Turbulence

• Aortic and arterial dilatation – aneurysm causes local stasis
• Acute Myocardial infarction –in the form of complication –
anuerysm of non contractile myocardium – mural thrombi
• Rheumatic aortic stenosis
• Polycythemia vera – hyperviscosity
• Sickle cell disease – occlusion
 Types of thrombus

1. Arterial or cardiac thrombi/mural thrombi :at site of turbulence

or endothelial injury
2. Venous thrombi – at the site of stasis
3. Vegetation – thrombi on heart valves
• Arterial thrombi grow retrograde to the blood flow
• Venous thrombi grow towards the blood flow
• Both propagate towards heart

• Line of Zahn :laminationsof light stain part ( formed by fibrins and

platelets ) and dark stain part ( formed by RBC) , only seen in
flowing blood – in antemartem clot ,not in post martem clot
 Types of thrombus

• Coronary ,cerebral and femoral arterial thrombus

• Venous thrombus in lower extremities

• Postmartem thrombus :
 Most gelatenous
 Chicken fat appearance
 Not attached to the underlying vessels wall
 Fate of thrombus

1. Propagation: Thrombi accumulate additional platelets and fibrin

2. Embolization:Thrombi dislodge and travel to other sites .
[Link]: Dissolution is the result of fibrinolysis, which can lead to
the rapid shrinkage and total disappearance of recent thrombi with
effective therapeutic administration of fibrinolytic thrombosis only
when given during the first few hours of a thrombotic event.
4. Organization and recanalization: Older thrombi become organized
by the in growth of endothelial cells, smooth muscle cells, and
fibroblasts . Capillary channels eventually form that reestablish the
continuity of the original lumen, albeit to a variable degree.
Continued recanalization may convert a thrombus into a smaller
mass of connective tissue that becomes incorporated into the
vessel wall.
 Definition of Embolism

• An embolus is a detached intravascular solid, liquid, or

gaseous mass that is carried by the blood from its point of
origin to a distant site, where it often causes tissue
dysfunction or infarction

• Emboli travel through the blood until they encounter vessels

too small to permit further passage, causing partial or
complete vascular occlusion.
 Types of Embolism

1. Pulmonary embolism – saddle emboli

2. Systemic thromboembolism- atherosclerotic/cholesterol
emboli
3. Fat and marrow Embolism
4. Air embolism
5. Amniotic fluid ambolism
6. Foreign bodies emboli
7. Paradoxical embolism – emboli pass from right side of heart
to left side of heart through the ventricular or atrial septal
defect
 Sequele of Embolism

• Deep vein thrombosis (DVT) in leg vein travel to the lungs

cause Pulmonary embolism (PE)
• PE – silent (60-80%); sudden death , cardiovascular collapse ,
right heart failure , corpulmonale , pulmonary hypertension .
• Atherosclerotic emboli – intraventricular infarct , brain
ischemic attack
• Fat embolism in long bone fracture, burn and soft tissue
trauma – pulmonary infarction , pulmonary insufficiency ,
neurologic symptoms , anemia , thrombocytopenia
• Cardiac by pass surgery , laparoscopic ,chest wall injury,scuba
diving , neurosurgery – air embolism – pulmonary distress ,
decompression sickness
 Sequele of Embolism

• Amniotic fluid embolism in pregnancy – sudden death ,

pulmonary edema , diffuse alveolar damage , permanent
neurological deficit

• Systemic embolism arise from

arteries ,intracardiac ,aneurysm ,valvular vegetation

• Major site for embolism : lower extrimities , brain , intestine ,

kidneys and spleen
 Definition of Infarction

• An infarct is an area of ischemic necrosis caused by occlusion

of either the arterial supply or the venous drainage.

• Diminished blood supply – cellular adaptation –

reversible ,then irreversible cell injury , in form of necrosis

• Blockage of artery – ischemia – infarction

• Blockage of vein – slow down the circulation – congestion

rather than infarction
 Examples of infarction

1. Myocardial infarction – occlusion of coronary arteries or its

branches

2. cerebral infarction

3. Pulmonary infarction – red color

4. Bowel infarction

5. Extremities infarction (gangrene) – diabetes

 Causes of infarction

• Thrombosis or embolism in arterial supply

 Local vessels spasm
 Compression of artery by tumor
 Torsion of artery – bowel or testicular /ovary
 Rupture of vessels in trauma
 Vessels trap in hernial sac
 Compression of artery by odema fluid in anterior
compartment syndrome
• Venous occlusion - bypass channel development -
congestion in most of tissue
• Infarction due to venous occlusion in those organ only which
have one efferetn vein with no colateral supply such as testis
and ovary
 types of Infarction

• Infarcts are classified according to

1. color : red /pale infarct
2. Age : fresh /old infarct
3. presence or absence of infection : septic /bland infarct

 Red infarct occur following venous occlusion in spongy tissue like

lung and in organ with dual blood supply such as liver
 Pale infarct in solid organ with end artery such as heart , spleen
and kidney
 Septic infarct from the infected vegetation from heart valve ,
microbes seed necrotic tissue
 Morphology of infarction

• Wedge shape with narrow end and broad base /end

• Apex of wedge located at site of occlusion
• Fresh infarct show poorly defined margin
• Old infarct show well defined margin due to congestion
around the infarct . Congestion develop due to inflammation
 Factor affecting infarction

1. Anatomy :
 dual blood supply organ such as lung and liver –less chance of
infarction
 End artery supply organ such as kidney and spleen – more of
infarction
2. Rate of occlusion – rapid process – more chance of infarction
Slow and gradual process – collateral circulation develop ,less chance
of infarction
3. Tissue vulnerability to hypoxia :
Neuron ischemia – in 3- 4minutes
Myocardial ischemia in 30-40 minutes
4. Hypoxemia – decrease in oxygen level in blood increases the
chances and extent of infarc tion