Lecture 5

General Pathology 2022

Derangement of homeostasis and

hemodynamics II
Prepared by: Mohammed Taha - Lawez Araz
– Huseen Hirmz – Prusha Aso – Ramiar
Akram – Rezheen Aryan
Circulatory disturbances of obstructive nature
Thrombosis
Thrombosis is the process of formation of solid mass in circulation from the constituents of flowing blood; the
mass itself is called a thrombus. In contrast, a blood clot is the mass of coagulated blood formed in vitro e.g. in a
test tube.
 Haematoma is the extravascular accumulation of blood clot e.g. into the tissues. Haemostatic plugs are the blood
clots formed in healthy individuals at the site of bleeding e.g. in injury to the blood vessel. In other words,
haemostatic plug at the cut end of a blood vessel may be considered the simplest form of thrombosis. Haemostatic
plugs are useful as they stop the escape of blood and plasma, whereas thrombi developing in the unruptured
cardiovascular system may be life-threatening by causing one of the following harmful effects:
1. Ischaemic injury. Thrombi may decrease or stop the blood supply to part of an organ or tissue and cause
ischaemia which may subsequently result in infarction. 2. Thromboembolism. The thrombus or its part may get
dislodged and be carried along in the bloodstream as embolus to lodge in a distant vessel.
Thrombosis:- formation of a solid mass in the circulation
-> the mass is called thrombus
-> blood clot:- solid mass of coagulated blood
-> Haematoma:- extravascular accumalation of blood clot
-> Haemostatic plug:- blood clot in a healthy individual at site of bleeding, ( useful in prevention of loss of blood and plasma)
but Raptured
->Thrombi ( blood clot formation in unruptured cardiovascular system) can cause:

1. Ischemic injury:- due to low blood supply to tissue and organ

2. Thromboembolism:- the thrombus may be transported through bloodstream and accumulate in another region
• Thrombosis (Thrombi): is the process of the formation of blood clot
• Different terms in medicine are used to describe blood clot, where the blood clot is occurred.
• Blood clot is usually used in the lab, when the blood is clotted within a test tube, this is a type of blood forming. When blood
is taken and put inside the tubes without heparin, after 5 mins they will clot (in vitro)
• Blood clot is possible to be produced, when the blood escapes the blood vessels, and is released into the tissues, it is called
hematoma, so hematoma is a blood clot formation outside the blood vessel.
• The third term is hemostatic plug, is a blood clot formation, when blood vessel is ruptured, so as to seal the wound a clot
forms which is called hemostatic plug.
• Another factor is thrombi, which is the blood clot formation in any non-ruptured blood vessel.
• Hematoma is blood clot in the tissue when blood comes out from the blood vessel
• Blood clot is normally used in lab (in vitro), such as when blood clots in a tube
• Hemostatic plug is when a blood vessel has ruptured and the wound need to be sealed (wound healing) and prevent escape
of blood
• But in case of thrombi, which is an abnormal condition, bleeding does not occur but clot still forms. In the blood vessels
there is no any rupture or bleeding, but blood clot formation occurs, and this result in 40 percent of deaths around the world,
due to thrombi and embolism.
 Pathophysiology
Since the protective haemostatic plug formed as a result of normal haemostasis is an example of thrombosis, it is
essential to describe thrombogenesis in relation to the normal haemostatic mechanism. Human beings possess inbuilt
system by which the blood remains in fluid state normally and guards against the hazards of thrombosis and
haemorrhage. However, injury to the blood vessel initiates haemostatic repair mechanism or thrombogenesis.

Virchow described three primary events which

predispose to thrombus formation (Virchow’s
triad): endothelial injury, altered blood flow, and
hypercoagulability of blood. To this are added the
processes that follow these primary events:
activation of platelets and of clotting system.

The main mechanism which increases the risk of blood clotting or thrombi is in endothelial injury, which is alteration in the blood
flow, hypercoagulability of the blood, and beside this, activation of the platelet and the clotting system will increase the risk of
thrombus, or blood clot formation.
1. Endothelial injury. The integrity of blood vessel wall is important for maintaining normal
blood flow. An intact endothelium has the following functions:
i. It protects the flowing blood from the thrombogenic influence of subendothelium. ii. It
elaborates a few anti-thrombotic factors (thrombosis inhibitory factors) e.g. a. Heparin-like
substance which accelerates the action of antithrombin III and inactivates some other clotting
factors.
b. Thrombomodulin which converts thrombin into activator of protein C, an anticoagulant.
iii. It can release a few prothrombotic factors which have procoagulant properties (thrombosis
favouring factors) e.g.
a. Von Willebrand factor that causes adherence of platelets to the subendothelium.
b. Platelet activating factor which is activator and aggregator of platelets.
Vascular injury exposes the subendothelial connective tissue (e.g. collagen, elastin,
fibronectin, laminin and glycosaminoglycans) which are thrombogenic and thus plays
important role in initiating haemostasis as well as thrombosis. Injury to vessel wall also causes
vasoconstriction of small blood vessels briefly so as to reduce the blood loss.
Endothelial injury is of major significance in the formation of arterial thrombi and thrombi
of the heart, especially of the left ventricle. A number of factors and conditions may cause
vascular injury and predispose to the formation of thrombi. These are as under: ▪
Endocardial injury in myocardial infarction, myocarditis, cardiac surgery, prosthetic valves.
▪ Haemodynamic stress in hypertension.
▪ Diabetes mellitus.
▪ Endogenous chemical agents such as hypercholesterolaemia, endotoxins.

▪ Exogenous chemical agents such as cigarette smoke.

 Blood vessels has endothelial layer, which has many functions. Some of the endothelial layer function is the:
✓ 1- releasing of some factors which prevent the blood clot formation
✓ 2- and at the same time endothelial layer is able to produce other factors that is important for blood clot formation.
Endothelial layer is important for:
✓ 1- prevention of interaction between platelet and subendothelial layer. After the endothelial layer is the subendothelial
layer which can interact easily with the platelets. So, the endothelial layer acts as a barrier to prevent this interaction
✓ 2- Antithrombotic factors are released by the endothelial layer, for example, antithrombin 3 prevents the process of blood
clot formation,
✓ 3- Production of chemical compounds (prothrombin factors), which are important to activate the process of blood clot
formation during bleeding.

• Von Willebrand factor is an important protein which is secreted by endothelial cells, this protein is important because it works
like a bridge between platelet and subendothelial layer. It enhances the interaction between platelet and subendothelial cells
• Platelet activated factor is also secreted by endothelial cells which is important in activation and aggregation of platelet, in
which this aggregation is important in the process of hemostasis. So, any problem in the endothelial layer will increase the risk of
blood clotting because platelet can interact with the subendothelial layer.
Some factors leading the to injury of the endothelial layer:
• 1- endocardial injure
2- myocardial fracture
3- hemodynamic stress
4- diabetic mellitus
5- endogenous chemicals such as cholesterol in blood
6- exogenous chemicals in those with diabetes mellitus because there is a excessive sugar in the blood which will accumulates
on the blood vessel wall and increases the risk of blood vessel damage.
2. Role of platelets. Following endothelial cell injury, platelets come to play a
central role in normal haemostasis as well as in thrombosis.
i. Platelet adhesion. The platelets in circulation recognize the site of endothelial injury and adhere
to exposed subendothelial collagen (primary aggregation); von Willebrand’s factor is
required for such adhesion between platelets and collagen.
ii. Platelet release reaction. The activated platelets then undergo release reaction by which the
platelet granules are released to the exterior.
• As a sequel to platelet activation and release reaction, the phospholipid complex platelet
factor 3 gets activated which plays important role in the intrinsic pathway
of coagulation.
iii. Platelet aggregation. Following release of ADP (adenosine diphosphate), a potent platelet
aggregating agent, aggregation of additional platelets takes place (secondary aggregation).
This results in formation of temporary haemostatic plug. However, stable haemostatic plug is
formed by the action of fibrin, thrombin and thromboxane A2.
• Platelet is another important factor which plays an important role in the process of blood clot
formation. And beside this they also increase the risk of thrombosis.
• Platelet itself has some specific functions which has role in maintenance of the mechanism of
hemostatic plaque formation.
• Any abnormality in platelet results in activation of several enzyme and protein which has role in
formation of blood clot, or sometime the strength of the platelet decreases and cannot form plague
• Platelet helps in formation of thrombosis, as mentioned before, when endothelial injury is present,
platelets become activated, once they becomes activated some modulators are being secreted at
the site of injury which enhances he mechanism of aggregation of the platelets which then results in
activation of clotting factors
 2. Role of
coagulation
system
Coagulation
mechanism is the
conversion of the
plasma fibrinogen
into solid mass of
fibrin. The
coagulation system
is involved in both
haemostatic process
and thrombus
formation.
Coagulation system; the process of hemostasis is controlled by two mechanisms: intrinsic and extrinsic.
Number of proteins (different types of proteins) are regulating the process of hemostasis and at the same time increasing the risk of
thrombosis. It is the mechanism of conversion of plasma fibrinogen to fibrin.
The figure shows the schematic representation of the cascade of intrinsic (blood) pathway, the
extrinsic (tissue) pathway, and the common pathway leading to formation of fibrin polymers.
i. In the intrinsic pathway, contact with abnormal surface leads to activation of factor XII
and the sequential interactions of factors XI, IX, VIII and finally factor X, alongwith
calcium ions (factor IV) and platelet factor 3.
ii. In the extrinsic pathway, tissue damage results in the release of tissue factor or
thromboplastin. Tissue factor on interaction with factor VII activates factor X. iii. The common
pathway begins where both intrinsic and extrinsic pathways converge to activate factor X
which forms a complex with factor Va and platelet factor 3, in the presence of calcium ions.
This complex activates prothrombin (factor II) to thrombin (factor IIa) which, in turn, converts
fibrinogen to fibrin. Initial monomeric fibrin is polymerised to form insoluble fibrin by
activation of factor XIII.
 Regulate 2 pathways:

Intrinsic:- vascular damage due to a factor present in blood/ slow response

Extrinsic:- vascular damage due to an external factor/ fast response

Regulation of coagulation system. The blood is kept in fluid state normally and coagulation
system kept in check by controlling mechanisms. These are as under:
a. Protease inhibitors. These act on coagulation factors so as to oppose the formation of
thrombin e.g. antithrombin III, protein C, C1 inactivator, α1-antitrypsin, α2-macroglobulin. b.
Fibrinolytic system. Plasmin, a potent fibrinolytic enzyme, is formed by the action of
plasminogen activator on plasminogen present in the normal plasma. Two types of
plasminogen activators (PA) are identified:
▪ Tissue-type PA derived from endothelial cells and leucocytes.
▪ Urokinase-like PA present in the plasma. Plasmin so formed acts on fibrin to destroy the
clot and produces fibrin split products (FSP).
• When intrinsic pathway becomes activated? If there is an injury inside of the blood vessels.

• 2 types of rupture are possible to occur. When an internal factor causes damage to the blood vessel and the blood clot

that forms there due to the coagulative factors is called intrinsic pathway. But when the blood vessels are ruptured

due to external factors then extrinsic pathway is activated.

• Those two factors are later on undergoing the common pathway which is activation of thrombin that has role in

converting fibrinogen into fibrin in which the fibrin is important to produce the blood clot.

• Some individuals have problem in those factors such as factor V which is important in converting prothrombin to

thrombin (latent factor). Any mutation in factor V will result in secretion of excess protein (factor V), thus the

mechanism oof thrombin formation rises and results in formation of excess fibrin which will affect blood clotting

formation

• Another mechanism is fibrinolytic system. When bleeding occur, hemostatic plague forms so that healing can occur.

After that the clot needs to be removed via fibrinolytic system. Plasminogen will produce plasmin which will degrade

the fibrin. If any individual has problem in this system, so the clot won’t be fully removed.
 4. Alteration of blood flow.

Turbulence means unequal flow while stasis means slowing.

i. Normally, there is axial flow of blood in which the most rapidly-moving central stream
consists of leucocytes and red cells. The platelets are present in the slow-moving laminar
stream adjacent to the central stream while the peripheral stream consists of most slow
moving cell-free plasma close to endothelial layer.
ii. Turbulence and stasis occur in thrombosis in which the normal axial flow of blood is
disturbed. When blood slows down, the blood cells including platelets marginate to the
periphery and form a kind of pavement close to endothelium (margination and
pavementing). While stasis allows a higher release of oxygen from the blood, turbulence
may actually injure the endothelium resulting in deposition of platelets and fibrin.
Formation of arterial and cardiac thrombi is facilitated by turbulence in the blood flow,
while stasis initiates the venous thrombi even without evidence of endothelial injury.
Alteration of the blood flow; normally there is an axial flow of the blood. When blood goes via blood vessel, RBC and WBC
are moving rapidly at the center of the vessel (central stream) whereas platelet is moving at a lower speed. And at the peripheral,
plasma is moving at a lower speed.
• Central stream: RBC and WBC
• Adjacent to central stream: Platelets
• Peripheral stream: Plasma
- This is very important to reduce the friction between the blood and blood vessel wall, at the same time it is important to
prevent the direct interaction between the blood cells (RBC, WBC, platelet) and the blood vessel wall.
- This is how normally blood flows through the blood vessels, no interaction happens between blood cells and blood vessel
walls, if blood cells interact with endothelial cell layer of blood vessels, it will cause injury.
- This flow may be disturbed, and when this occurs the platelet can easily interact with the endothelial layer.
- Statis: blood flow slows down. When stasis occur, platelet slows down and may be distributed. Sometimes it may not be
related to the movement of the blood and may be due to an imbalance in organization of the cells, in this case they can interact
with the endothelial layer and cause injury

Factors that slow down the blood flow:

• Due to hypotension blood pressure decreases and heart rate may decrease, this will lead to slowing down of the blood flow.
• It may be a mental thing that goes back to normal in a couple of minutes or seconds (factoreki nafsi).
• Might be due to obstruction.
• Might be due to decrease in blood volume (hemorrhage, dehydration because of excessive diarrhea and vomiting will
decrease blood volume).
5. Hypercoagulability of blood. The occurrence of thrombosis in some conditions such as in
nephrotic syndrome, advanced cancers, extensive trauma, burns and during puerperium is
explained on the basis of hypercoagulability of blood. The effect of hypercoagulability on
thrombosis is favoured by advancing age, smoking, use of oral contraceptives and obesity.
Hypercoagulability may occur by the following changes in the composition of blood:
i. Increase in coagulation factors e.g. fibrinogen, prothrombin, factor VIIa, VIIIa and Xa.
ii. Increase in platelet count and their adhesiveness.
iii. Decreased levels of coagulation inhibitors e.g. antithrombin III, fibrin split products.
• -Due to increased coagulation factors like fibrinogen
• -Increase in platelets
• decreased level of coagulation inhibitors
• Hypercoagulability of blood: proteins working together in order to control the process of blood clot formation in the normal
condition. And in some abnormal conditions these factors are possible to be changed in the body.
• There are 2 groups: first group is pro and second group is anti.
• Pro is loss of factors like fibrinogen, prothrombin, 7,8 and 10 work as pro which increase the risk of blood clot formation.
• A lot of individuals have problem in having excess fibrinogen, thus there will be excssive bloo clump. This can be due to
genetic variation, lifestyle, other diseases, or alteration in those protein that that have role in the clotting process and prevent
blood clotting.

• Q/ Yake law 7alatanay ka normally qabili away ka thrombosis drus bkat u paywandi bam system’awa habet la kati pregnancy
ya ba taybati third trimester’y pregnancy, and dway la daykbuni mnalaka ba 2-3 mang law zamanaya afrataka la risk’y awaya
ka tushi thrombosis bet. Bochi?
• Answer: During labor rupture of the placenta and blood vessels will cause severe bleeding, the amount of coagulative factors
in the normal female body in not enough to stop this bleeding, this is why progestron and estrogen increases beforehand to
create enough coagulative factors to stop the bleeding when it happens.

• This is one of the things that the female body does to prepare for labor
• Bahoy zori rezhay coagulative factor’kan afrati dugyan agari away haya tushi jalda be ba hoy thrombosis
Predisposing Factors
A number of primary (genetic) and secondary (acquired) factors favour
thrombosis.

Primary (Genetic) factors: deficiency of antithrombin and ,mutation in factor Vs

Secondary (acquired) factors:
a) Risk factors: advanced age, prolonged bed-rest and cigarette
smoking b) Clinical conditions predisposing to thrombosis:
• Heart diseases (e.g. myocardial infarction and rheumatic mitral stenosis)
• Vascular diseases (e.g. atherosclerosis and varicosities of leg veins)
• Hypercoagulable conditions (e.g. polycythaemia, dehydration, nephrotic syndrome)
• Shock
• Tissue damage e.g. trauma, fractures, burns, surgery
• Late pregnancy and puerperium
• Certain drugs (e.g. anaesthetic agents, oral contraceptives).
Genetic (primary) factors:-

deficiency in genetic variation and mutation in a number of factors which increases the risk of the process of blood clot formation or having mutation in

those gene encoding proteins which are working as anti-blod clot formation will increases the risk of thrombosis

Acquired (secondary) factors

A. Risk factors:- age, and smoke

B. Clinical condition

• heart disease (myocardial infarction and rheumatic mitral stenosis)

• Vascular disease (atherosclerosis and varicosities of leg veins). Atherosclerosis is when a mixture of lipid, calcium, platelet, and connective

tissue bind with each other.

Varicosities of leg vein is dilation of blood vessel and increasing the risk of thrombosis

• Hypercoagulable conditions (e.g. polycythaemia, dehydration, nephrotic syndrome). Polycythemia is formation or large amount of blood cell

abnormally due to increases in number of PCV. Dehydration is escape of large amount of water from the body.

• Shock

• Tissue damage e.g. trauma, fractures, burns, surgery

• Drugs (anaesthetic agents, and oral contraception. Progestogen oral contraception affects blood clotting by increasing plasma fibrinogen and

the activity of coagulation factors. Anesthetic agents increases the risk of thrombosis, why? causes dilatation of the blood vessels in which blood
flow slows down so that blood clot is more suspectible
 Origin of Thrombi
Thrombi may arise from the heart, arteries, veins or in microcirculation.

I. Cardiac thrombi. Thrombi may form in any of the chambers of the heart and on the valve cusps.
They are more common in the atrial appendages, especially of the right atrium, and on mitral and aortic
valves called vegetations which may be seen in infective endocarditis and non-bacterial thrombotic
endocarditis. Cardiac thrombi are mural (non occlusive) as are the mural thrombi encountered in the
aorta in atherosclerosis and in aneurysmal dilatations. Rarely, large round thrombus may form and
obstruct the mitral valve and is called ball-valve thrombus. Agonal thrombi are formed shortly before
death and may occur in either or both the ventricles. They are composed mainly of fibrin.
Cardiac thrombosis:- during endocarditis cardiac thrombosis are mural (in walls).

• The thrombi that are produced within the heart is n form of mural thrombi.

• Mural thrombi does not completely block the heart (not occlusive), it may be produced on the valves or aorta. It reduces the flow of blood.

• Although it is very rare, but it is possible for the occlusive thrombi to be produced within the heart which is called ball-valve thromboses

Agonal thrombi: - one large, blood clot in heart before death ( in ventricles). It is formed within patient suffering from myocardial infarction (la kati

mawai mrdni kaseka rru adat). It blocks all the chambers of the heart.
II. Arterial and venous thrombi. The examples of major forms of vascular thrombi are as under:
 Arterial thrombi:
• Aorta: aneurysms, arteritis.
• Coronary arteries: atherosclerosis.
• Cerebral artery: atherosclerosis, vasculitis.
Venous thrombi:
• Veins of lower limbs: deep veins of legs, varicose veins.
• Pulmonary veins: CHF, pulmonary hypertension.
• Hepatic and portal vein: portal hypertension.

III. Capillary thrombi. Minute thrombi composed mainly of packed red cells are formed in the
capillaries in acute inflammatory lesions, vasculitis and in disseminated intravascular coagulation
(DIC).
• Artery thrombi: - in aorta, coronal and cerebral arteries

• Venous thrombi:- vein of lower limb, pulmonary, hepatic and portal vein.

• Capillary thrombi:- the thrombus occurs in capillary and obstruct the exchange of nutrient and gases.

• Individuals with DIC has problem with bleeding, either it won’t be controlled or it will take a longer time to be

controlled, why? because the number of coagulating factors has reduced since there is clotting in many places

• In some areas of the body, large amount of blood clotting is produced in the basis of those platelets and clotting factors

that are moving through the blood vessels. This will result in reduction of the platelets and clotting factors because they

are used in large concentration, that’s why once bleeding occur there is no enough platelet and clotting factor to control it

• Another mechanism is that, once clotting factor increases, the anti is reduced. In the body when two things are an

antagonist of each other, when one of them rises, the other reduces such as in case of insulin and glucagon. This situation

is same, when the blood clot forms, the anti is reduced.

Fate of Thrombus
The possible fate of thrombi can be as under:
1. Resolution. Thrombus activates the fibrinolytic system with consequent release of plasmin
which may dissolve the thrombus completely resulting in resolution. Usually, lysis is
complete in small venous thrombi while large thrombi may not be dissolved. Fibrinolytic
activity can be accentuated by administration of thrombolytic substances (e.g. urokinase,
streptokinase), especially in the early stage when fibrin is in monomeric form.

Resolution:- the human body can naturally dissolvethe formed thrombi and get rid of it and is removed

2. Organization. If the thrombus is not removed, it starts getting organised. Phagocytic cells
(neutrophils and macrophages) appear and begin to phagocytose fibrin and cell debris. The
proteolytic enzymes liberated by leucocytes and endothelial cells start digesting coagulum.
Capillaries grow into the thrombus from the site of its attachment and fibroblasts start
invading the thrombus. Thus, fibrovascular granulation tissue is formed which subsequently
becomes dense and less vascular and is covered over by endothelial cells.
 ▪ The thrombus in this way is excluded from the vascular lumen and becomes part of vessel
wall. The new vascular channels in it may be able to re-establish the blood flow, called
recanalisation. The fibrosed thrombus may undergo hyalinisation and calcification e.g.
phleboliths in the pelvic veins.

Organization:- if it is not removed, the thrombi gets organized. It accumulates in the wall of BV.
• This stimulates phagostic cells -> inflammation-> normal cells are damaged-> fibrosis

3. Propagation. The thrombus may enlarge in size due to more and more deposition from the
constituents of flowing blood. In this way, it may ultimately cause obstruction of some
important vessel.

Propogation:- the size of thrombi increases and obstructs the blood vessel making it smaller and alters the normal flow of the
blood vessel
 4. Thromboembolism. The thrombi in early stage and infected thrombi are quite friable and
may get detached from the vessel wall. These are released in part or completely in
bloodstream as emboli which produce ill-effects at the site of their lodgement.

Thromboembolism:- the thrombi is detached from original site and deported to another region and causes obstruction in
another part of the body.
• When the thrombus is produced, it may lead to different consequences. The first one is resolution, there is possibility of large
amount of blood clot to be produced, but the body has the ability to control it and dissolve it, this process is known as resolution.
When thrombi are produced, the body of the individual degrade and remove it. May be due to some conditions, the thombi is not
removed if the thrombi are large in size.
• Thrombi is normally formed on the blood vessel walls. At the beginning, it is small and size and increases gradually. This first
mechanism is resolution of the thrombi in which the size is small and there is no any sign and symptom. This can occur in
normal daily life within the body of the individuals
• The second mechanism is interaction of the thrombi with the endothelia layers. Since its size has become larger, so it is not
easily controlled and results in formation of acute inflammation. Which means there will be accumulation of large amount of the
WBC. This causes formation of new blood capillary so as to supply the cells. Even though they are located within the blood
vessels, but still won’t they receive nutrition form it.
• Later on, the connective tissue (fibroblast) interferes, and after that they will be surrounded by the endothelial cells. When this
occurs, it means that the thrombi become part of the blood vessel which is said to be organization. These steps are following
each other without the any sign and symptoms. Even the blood vessels do not cause any pain, or it will be moderate.
• Another mechanism that may occur is propagation, in which the blood vessel will be obstructed completely because of the
gradual increase in the size of the mass up to a point that can obstruct the blood vessel.
• Why thrombosis is not very dangerous in organs like liver and lung compared to other organs such as kidney or spleen
in which thrombosis is very dangerous? La bar away hanek organ wakw liver w lung dual secretory system’yan haya, wata
agar la yakek la source’kanawa thrombosis ru bdat w obstruct bbet, heshta source’i try haya tawak supply organ’aka har
bardawam bbet, bo nmwna the liver receives a blood supply from two sources. The first is the hepatic artery which delivers
oxygenated blood from the general circulation. The second is the hepatic portal vein delivering deoxygenated blood from the
small intestine containing nutrients.
• Another thing that’s possible to happen is thromboembolism. When the thrombi are produced from the primary site, a part
detaches from it and causes obstruction in secondary site.
Clinical Effects
These depend upon the site of thrombi, rapidity of formation, and nature of thrombi.
1. Cardiac thrombi. Large thrombi in the heart may cause sudden death by mechanical
obstruction of blood flow or through thromboembolism to vital organs.
2. Arterial thrombi. These cause ischaemic necrosis of the deprived part (infarct) which
may lead to gangrene. Sudden death may occur following thrombosis of coronary artery.
3. Venous thrombi (Phlebothrombosis). These may cause following effects:
thromboembolism, oedema of area drained, poor wound healing, etc…
4. Capillary thrombi. Microthrombi in microcirculation may give rise to disseminated
intravascular coagulation (DIC).
• Cardiac:- large thrombi produced in heart which may cause sudden death

• Arterial:- increases risk of ischemic necrosis of infected region --> gangrene ---> sudden death

• Venous:- may cause thromboembolism, and odema in region

• Capillaries:- increases the risk of disseminated intravascular coagulation ( DIC)→ drustbuni blood clot’i bchuk systematically→ keshai

bleeding abe chunka blood clot’i bchuk drust bua yani accumulation’i platelet is used up for this accumulation w rezhai platelete used for

clotting factors kam abetawa.

• Grossly:- arterial thrombi:- white and mural

• Venous thrombi:- red and occlusive

Grossly, thrombi may be of various shapes, sizes and composition depending upon the site of
origin. Arterial thrombi tend to be white and mural while the venous thrombi are red and
occlusive. Mixed or laminated thrombi are also common and consist of alternate white and red
layers called lines of Zahn. Red thrombi are soft, red and gelatinous whereas white thrombi
are firm and pale.
Microscopically, the composition of thrombus is determined by the rate of flow of blood i.e.
whether it is formed in the rapid arterial and cardiac circulation, or in the slow moving flow
in veins. The lines of Zahn are formed by alternate layers of light-staining aggregated platelets
admixed with fibrin meshwork and dark-staining layer of red cells. Red (venous) thrombi have
more abundant red cells, leucocytes and platelets entrapped in fibrin meshwork. Thus, red
thrombi closely resemble blood clots in vitro.
 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. The vast
majority of emboli derive from a dislodged thrombus—hence the term thromboembolism.
Less commonly, emboli are composed of fat
droplets, bubbles of air or nitrogen,
atherosclerotic debris (cholesterol emboli), tumor
fragments, bits of bone marrow, or amniotic fluid.
Inevitably, emboli lodge in vessels too small to
permit further passage, resulting in partial or
complete vascular occlusion; depending on the
site of origin, emboli can arrest anywhere in the vascular tree.
• Embolism is the process by which emboli, a mass, travels through the bloodstream and lodges in a specific area in the body and increases the
risk of obstruction.
• Emboli is possible to be produced as a part of the thrombi blood clot which is produced in many parts of the body such as the vein, artery, the
heart. This part of the thrombi is moving through the circulatory system until it reaches an area where it can block the circulation.
 Thromboembolism
A detached thrombus or part of thrombus constitutes the most common type of embolism.
These may arise in the arterial or venous circulation:
Arterial (systemic) thromboembolism. Arterial emboli may be derived from the following
sources:
A. Causes within the heart (80-85%): These are mural thrombi in the left atrium or left ventricle,
vegetations on the mitral or aortic valves, prosthetic heart valves and cardiomyopathy.
B. Causes within the arteries: These include emboli developing in relation to atherosclerotic
plaques, aortic aneurysms, pulmonary veins and paradoxical arterial emboli from the
systemic venous circulation.

Arterial thromboembolism: - the emboli that is produced from left side of heart or aorta (blood arteries) is in the risk to be
distributed to all parts of the body. Because the left side of the heart pumps blood to all parts of the body.
Common sources and effects of systemic arterial emboli. It usually arises from the
left side of the heart or from major arteries. Usual consequence is either infarction or
gangrene at the site of lodgment
The effects of arterial emboli depend upon their size, site of lodgement, and adequacy of
collateral circulation. If the vascular occlusion occurs, the following ill-effects may result:
i. Infarction of the organ or its affected part e.g. ischaemic necrosis in the lower limbs (70-
75%), spleen, kidneys, brain, intestine.
ii. Gangrene following infarction in the lower limbs if the collateral circulation is
inadequate.
iii. Arteritis and mycotic aneurysm formation from bacterial endocarditis. iv. Myocardial
infarction may occur following coronary embolism. v. Sudden death may result from
coronary embolism or embolism in the middle cerebral artery.
• Emboli has many types, the first one is the thrombi embolism. 80% - 85% thrombi embolism is produced in the heart. Thus
the thrombus produced in the heart undergoes fragmentation, becomes small particles, and is then distributed. These
fragments are called emboli. This type becomes distributed throughout the body whereas the others might be produced in
the artery itself.
• The major problem with thrombus embolism is that the proteins become thrombus then emboli and finally thrombus emboli.
• A thrombus is produced in the blood vessels, the artery, of the heart, when attached to emboli and affects the lungs. It is
systemic, especially the ones produced in the left side of the heart, the thrombus embolism is ejected from the left side of the
heart, which pumps blood to the body hence the whole body is susceptible for the risk of emboli. Within all the organs in the
body, the lower limb is the most common place for emboli to reach.
• Q/ Why the lower limb is the most susceptible place for thrombus emboli? Why is the effect of thrombus embolism
is much greater compared to the other organs? Emboli are a part of thrombi which detaches from it and ejects from the
heart. If it is produced in the left ventricle, it will reach the entire body, the most common of these places which the emboli
mostly affect is the lower limb, why?
Some possible answers could be:
• Due to the pulling of gravity.
• Because it is the most distant area from the heart.
• Because there is a large amount of end arteries in the lower limb.
 Venous thromboembolism. Venous emboli may arise from the following sources: i.
Thrombi in the veins of the lower legs are the most common cause of venous emboli. ii.
Thrombi in the pelvic veins.
iii. Thrombi in the veins of the upper limbs.
iv. Thrombosis in cavernous sinus of the brain.
v. Thrombi in the right side of heart.
The most significant effect of venous embolism is obstruction of pulmonary arterial
circulation leading to pulmonary embolism described below.

• Venous thromboembolism: - Venous thrombi embolism is another type of embolism which is possible
to occur due to the fragmentation of thrombi inside the vein this time and not the heart.
• Thrombosis in the vein is common especially in the lower limb.
 Pulmonary Thromboembolism
Pulmonary embolism is the most common and fatal form of venous thromboembolism in which there is occlusion of
pulmonary arterial tree by thromboemboli. Pulmonary thrombosis as such is uncommon and may occur in pulmonary
atherosclerosis and pulmonary hypertension. Etiology.

The causes of pulmonary emboli are as

follows:
i. Thrombi originating from large veins of lower
legs (such as popliteal, femoral and iliac) are
the cause in 95% of pulmonary emboli.
ii. Less common sources include thrombi in
varicosities of superficial veins of the legs, and
pelvic veins such as periprostatic, periovarian,
uterine and broad ligament veins.

-> a type of venous thromboembolism

-> the thrombi comes from right side of heart
-> the thrombi block the area of the bifurcation of pulmonary artery -> saddle embolism
-> one large thrombi into smaller thrombi which affect smaller and other vessels -> multiple emboli
Pathogenesis. Detachment of thrombi from any of the above-mentioned sites produces a
thrombo-embolus that flows through venous drainage into the larger veins draining into right
side of the heart. If the thrombus is large, it is impacted at the bifurcation of the main
pulmonary artery (saddle embolus), or may be found in the right ventricle or its outflow tract.
More commonly, there are multiple emboli, or a large embolus may be fragmented into many
smaller emboli which are then impacted in a number of vessels, particularly affecting the
lower lobes of lungs. Rarely, paradoxical embolism may occur by passage of an embolus
from right heart into the left heart through atrial or ventricular septal defect. In this way,
pulmonary emboli may reach systemic circulation.
Consequences of pulmonary embolism.
Pulmonary embolism occurs more commonly as a complication in patients of acute or chronic
debilitating diseases who are immobilised for a long duration. Women in their reproductive
period are at higher risk such as in late pregnancy, following delivery and with use of
contraceptive pills. The effects of pulmonary embolism depend mainly on the size of the
occluded vessel, the number of emboli, and on the cardiovascular status of the patient. The
following consequences can result:
i. Resolution. Vast majority of small pulmonary emboli (60-80%) are resolved by fibrinolytic
activity. These patients are clinically silent owing to bronchial circulation so that lung
parenchyma is adequately perfused.
ii. Sudden death. a large embolus that blocks a major pulmonary artery can cause sudden
death.
iii. Pulmonary infarction. Obstruction of relatively smallsized pulmonary arterial branches
may result in pulmonary infarction.
iv. Pulmonary haemorrhage. Obstruction of terminal branches (end arteries) leads to central
pulmonary haemorrhage. The clinical features are haemoptysis, dyspnoea, and less
commonly, chest pain due to central location of pulmonary haemorrhage. Sometimes, there
may be concomitant pulmonary infarction.
v. Pulmonary hypertension, chronic cor pulmonale and pulmonary arteriosclerosis. These
are the sequelae of multiple small thromboemboli undergoing healing rather than resolution.
Pulmonary thromboembolism

• Pulmonary thrombi embolism is one of the most dangerous types of embolism because it affects the lungs. Usually, when
emboli are produced it can either be related to the veins or the left side of the heart (arteries). Emboli are also possible to be
produced in the large veins of the lower limb.
• 95% of pulmonary emboli are due to the emboli coming from the lower limb. The superficial veins compose the remaining
5%.
• When an embolus is produced inside a vein, it directly enters the right side of the heart, right atria, right ventricle and then
into the lungs. These emboli produced could sometimes affect the heart and cause right side heart failure or enter the
pulmonary artery where it bifurcates into two branches one into each lung, sometimes the emboli may block both of these
branches or one of them, according to the size of the emboli. This condition is very dangerous and fatal.

Consequences of pulmonary embolism:

• Resolution: same as with thrombosis, 60% - 80% of these cases can be treated without any complications.
• Sudden Death: especially when it blocks the pulmonary arteries.
• Pulmonary Infarction: is possible to be seen when the small blood vessels, which supply blood to different parts of the
heart, are obstructed by the emboli.
• Pulmonary Hemorrhage: because high pressure is produced in the veins
• Q/ Why when the obstruction is in the artery, there is no hemorrhage, hemorrhage is low, while if the obstruction is in

the veins, hemorrhage is present and high?

Some possible answers:

1. The blood vessel walls are different, veins are smaller than arteries.

2. Veins are thin, arteries are thick.

• Q/ What takes place before hemorrhage (rupture) if obstruction occurs in the veins?

• Accumulation of blood in veins, while there is no accumulation of blood in the arteries.

• Obstruction occurs in both the veins and arteries, but in arteries the color changes into a pale one while in veins the

color appears to be red, why?

• Due to the accumulation of blood. The accumulation of blood in veins forms a pressure on the veins leading to its rupture because

of the continues blood supply reaching the area. But in arteries, when the artery is blocked, the blood circulation is not interrupted

and is redistributed into other areas through other vessels.

 Fat Embolism
Obstruction of arterioles and capillaries by fat globules constitutes fat embolism. If the obstruction in the circulation is by
fragments of adipose tissue, it is called fat-tissue embolism. Etiology. Following are the important causes of
fat embolism:
i. Traumatic causes: Trauma to bones is the most common cause of fat embolism e.g. • in fractures of long
bones leading to passage of fatty marrow in circulation, after orthopaedic surgical procedures etc.
• Trauma to soft tissue e.g. laceration of adipose tissue
and in puerperium due to injury to pelvic fatty tissue.
ii. Non-traumatic causes: Extensive burns, diabetes
mellitus, fatty liver, pancreatitis, inflammation of bones
and soft tissues, extrinsic fat or oils introduced into the body.

→obstruction of arteriole and capillaries by fat globules (adipose tissue).

• The thrombi are made up of fat.
• For example, in case bone fracture, the fat droplets are distributing via blood, and the lymphocytes are being degraded in large
concentration
• At anyplace, where there is large amount of fat at the soft tissue or bone, when there is a damage either due to surgery or
anything that allow entrance of fat into the blood, embolism will result
Air Embolism
Air embolism occurs when air is introduced into venous or arterial circulation.

Causes
i. Operations on head and neck, and trauma. The accidental opening of a major vein of the neck like jugular,
or neck wounds involving the major neck veins, may allow air to be drawn into venous circulation.
 ii. Obstetrical operations and trauma. During childbirth by normal vaginal delivery, caesarean section,
abortions and other procedures, fatal air embolism may result from the entrance of air into the opened-up
uterine venous sinuses and endometrial veins.
iii. Intravenous infusion of blood and fluid. Air embolism may occur during intravenous blood or fluid
infusions if only positive pressure is employed.
iv. Angiography. During angiographic procedures, air may be entrapped into a large blood vessels.
v. Cardiothoracic surgery and trauma. Arterial air embolism may occur following thoracic operations,
thoracocentesis, rupture of the lung, penetrating wounds of the lung, etc.

Air embolism
• Air accumulates in arteries or veins
• Air bubble is possible to increase the risk of the obstruction especially in the very small blood vessels.
• Air bubble may be produced in those who are undergoing heart surgery, chest surgery or those who are receiving drugs
through intravenous injection. Those bubbles may be able to block the small blood vessels, so there should not be any
bubble in case of intravenous injection. In case of intramuscular is is somehow acceptable.
 Amniotic Fluid Embolism
This is the most serious, unpredictable and unpreventable cause of maternal mortality. During labour (uterine
contraction) and in the immediate postpartum period, the contents of amniotic fluid may enter the
uterine veins and reach right side of the heart resulting in fatal complications. The mechanism by which
these amniotic fluid contents
enter the maternal circulation is not clear. Possibly, they
gain entry either through tears in the myometrium and
endocervix, or the amniotic fluid is forced into uterine
sinusoids by vigorous uterine contractions. The clinical
syndrome of amniotic fluid embolism is characterised
by the following features: Sudden respiratory distress
and dyspnea, deep cyanosis, cardiovascular shock,
This Photo by Unknown Author is licensed under CC
convulsions, coma, and unexpected death.

• This is a very rare condition.

• Daikaka lawanaya la katy la daikbuni mnalakaya ba hoi aw rupture’ay ka drust abe la artery’akana, i7timala amniotic fluid
bcheta naw blood vessel’akanawa, am 7allata zor dagmana, ballam zor fatal’a ka ru bdat, cardiovascular shock drust aka.
 Atheroembolism
Atheromatous plaques, especially from aorta, may get eroded to form atherosclerotic emboli which are
then lodged in medium-sized and small arteries. These emboli consist of cholesterol crystals, hyaline
debris and calcified material, and may evoke foreign body reaction at the site of lodgement.

• Atheromatous plaque (cholesterol crystal, and calcified materials) gets trapped in arteries
• Emboli is sometime called atheroembolism. Because there ia a mixture of some particles on the blood vessel wall of the
arteries which may cause emboli

Tumour Embolism
Malignant tumour cells invade the local blood
vessels and may form tumour emboli to be lodged
elsewhere, producing metastatic tumour deposits.
Notable examples are clear cell carcinoma of
kidney, carcinoma of the lung, malignant melanoma etc.
 Infarction
Infarction is the process of tissue necrosis resulting from some form of circulatory
insufficiency; the localised area of necrosis so developed is called an infarct.
Etiology. All the causes of ischaemia discussed above can cause infarction. There are a few other
noteworthy features in infarction:
Most commonly, infarcts are caused by interruption in arterial blood supply, called ischaemic
necrosis. Less commonly, venous obstruction can produce infarcts termed stagnant hypoxia.
Generally, sudden, complete, and continuous
occlusion (e.g. thrombosis or embolism) produces
infarcts. Infarcts may be produced by nonocclusive
circulatory insufficiency as well e.g. incomplete
atherosclerotic narrowing of coronary arteries may
produce myocardial infarction due to acute coronary
insufficiency
 Factors that Determine the Outcome of an Infarct
The outcome of vascular occlusion may range from no or minimal effect to the death of a tissue
or individual. The major factors that determine the outcome of infarct are:

1. Nature of the vascular supply:

• Dual/parallel blood supply: Organs or tissues with double or parallel blood supply are less
likely to develop infarction, e.g. lung, liver, hand and forearm.
• End-arterial blood supply: Kidney and spleen has blood supply, which are end-arteries with little
or no collaterals. Obstruction of vessels in these organs usually causes tissue death and
infarction.

kidney lagal spleen zyatr karigar abe ba infarction wak la lung w liver.
 2. Rate of occlusion: Slow occlusion is less likely to produce infarction than rapid occlusion.
This is because it provides time to develop alternate perfusion pathways.

Q/ If decrease in the blood supply happens gradually is less dangerous than if it happens rapidly, why? Infarction wak
mechanism farqakai lagal ischemia awaya, ischemia decrease’y blood supply’a ballam infarction stop blood supply’a ( ba tawawy
blood supply awastene), ka blood supply wasta necrosis ru aya, jory necrosis’aka coagulative’a.

Why slow occlusion is less effective than rapid occlusion?

Ans/ Agar blood supply gradually kam betawa new blood vessel drust abe, dway blood la blood vessel’a tazakan war agret. Balam
agar rapidly yaksar block bet, am mechanism’a ru naya.

Q/Bochy jalday dll la kasy bataman zyatr tahamuli aka wak la ganj?
Ans/ labar away blood vessel’akan la kasy bataman zyatra wak la kaseki ganj. Blood vessel’akan wakw raqam zyatra

3. Vulnerability of tissue to hypoxia:

• Neurons are highly sensitive to hypoxia. They undergo necrosis even if the blood supply
is occluded for 3 to 4 minutes.
• In heart, myocardial cells are also quite sensitive to hypoxia, but less sensitive than
neurons. Myocardial cells die after only 20 to 30 minutes of ischemia.
 4. Oxygen content of blood: In a normal individual, partial obstruction of a small vessel
may not produce any effect, but in a patient with anemia or cyanosis same may produce
infarction.

Q/ Agar dw shaxs hardwkyan tushi ischemia bn. Yakekian anemia’y be la asasa, kaseki kayan normal bet, karigaryakai lasar
kamian zortr abet?

Ans/ Anemia. Kasek ka anemia’y be ya3ni already cell’akany oxygen’y pewistyan nagate, karygaryaka lama zyatr darakawe, xrap
abe ba xraptr, bas bashaka abe ba xrap.

Types of infarcts. Infarcts are classified depending upon different

features:
1. According to their colour:
• Pale or anaemic, due to arterial occlusion and are seen in compact organs e.g. in the kidneys, heart, spleen.

Produced due to obstruction of the arteries

• Red or haemorrhagic, seen in soft loose tissues and are caused either by pulmonary arterial obstruction
(e.g. in the lungs) or by arterial or venous occlusion (e.g. in the intestines).

Produced due to venous obstruction

2. According to their age:

• Recent or fresh
• Old or healed
3. According to presence or absence of infection:
• Bland, when free of bacterial contamination
• Septic, when infected.
Morphologic features. Some general morphological features of infarcts are common to infarcts of
all organ sites.
Grossly, infarcts of solid organs are usually wedgeshaped, the apex pointing towards the occluded
artery and the wide base on the surface of the organ. Infarcts due to arterial occlusion are generally
pale while those due to venous obstruction are haemorrhagic.
Most infarcts become pale later as the red cells
are lysed but pulmonary infarcts never become
pale due to extensive amount of blood. Recent
infarcts are generally slightly elevated over the
surface while the old infarcts are shrunken and
depressed under the surface of the organ.

Microscopically, the pathognomonic cytologic change in all infarcts is coagulative

(ischaemic) necrosis of the affected area of tissue or organ.
At the periphery of an infarct, inflammatory reaction is noted. Initially, neutrophils
predominate but subsequently macrophages and fibroblasts appear.
Eventually, the necrotic area is replaced by fibrous scar tissue, which at times may show
dystrophic calcification. In cerebral infarcts, the liquefactive necrosis is followed by gliosis i.e.
replacement by microglial cells distended by fatty material (gitter cells).