#26 ,, script patho ,, systemic thromboembolism

8/3/2019 #26 ,, script patho ,, Systemic Thromboembolism

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IN THE NAME OF ALLAH

Continue the previous lecture :

( Last few slides in slides # 3 )

Venous thrombosis :

We have the superficial and the deep vein thrombosis .the superficial

vein thrombosis usually happens in the saphenous system of the lower

limbs , usually accompanied by varicose pain or varicosities.

Manifestations of superficial vein thrombosis : local congestion, swelling

(edema), pain, tenderness, infections of overlying skin and development

of varicose skin ulcers. And once it`s compared to the deep type it`s

Rarely a source of embolism.

The deep vein thrombosis is the one that is more dangerous , it`s more

serious , it might lead to the production of pulmonary emboli . the

symptoms are edema , pain and tenderness .

Causes of deep vein thrombosis:

1. Occurs with stasis in the venous circulation due to heart failure

2. Sedentary life style, trauma , surgery and pain . Once the patient is

bedridden or is not moving a lot this might lead to stases.

3. Vascular injury with release of clotting factors and reduced tissue

plasminogen activators.

Some of the conditions leading to DVT include:

- Cancers, pregnancy, advanced age, prolonged bed rest, post-operative,late pregnancy, and postpartum.

- Congenital conditions such as Factor V mutation, antithrombin III

deficiency, protein C and S deficiency and defects in fibrinolysis.

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For the cardial and the artrial thrombosis the cause here is

Atherosclerosis .Miocardial Infarction (MI) , Rheumatic Fever (RF) will

lead to development of cardiac thrombosis. Once there is embolus in the

aorta there will be embolization and that will be discussed later.

Slides part 4

EMBOLISM, INFARCTION AND SHOCK

: is a detached intravascular solid, liquid, or gaseous massEmbolism

carried to a site distant from its point of origin .so once we say

embolism it doesn`t mean that it should be a thrombus, it might be other

substances.

Sourcesofemboli:

Thrombi (99%) (thromboembolism)

Atherosclerotic fragments cholesterol emboli*

Bubbles of air or nitrogen.*

Fat droplets.*

*Amniotic fluid.

*Bits of bone marrow.

*Tumor fragments

so the sequence of embolism is that this embolus will keep going into

the circulation unless or until it gets stuck in one of the small arteries or

veins . so once there issluggish movement it will either cause partial or

complete vascular occlusion , and this occlusion will either lead to

ischemia if it`s partial or to infarction if it`s complete obstruction .

Emboli lodge is either pulmonary or systemic circulation depending on

the type of embolism ; whether it`s venous or arterial type .

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Pulmonary thromboembolism

:Theetiology

deep vein thrombosis usually at the lower limbs .

we have 2 types one above the knee and the other is below the knee,

deep vein thrombosis that is below the knee is less harmful than the

one above the knee or in the pelvis . so once it`s above the knee it has

higher chance for thromboembolism .

Majority of cases are small emboli (60-80%) and clinically silent,

however if the size of embolus is a bet large this might lead to

appearance of symptoms . extremely large emboli or what we call the

sudden embolus might lead to a sudden death or what we call or

corpulmonale which is dilation and failure of right heart secondary to

pulmonary heart pressure.

the medium size emboli will lead to pulmonary hemorrhage but notinfarcts because the Lunghas double blood supply , one from the

pulmonary artery and the other is from the bronchial artery which is

part of the aorta so it`s in the non-oxygenized circulation and the

pulmonary artery origins from the right ventricle , so the main blood

supply is from the pulmonary artery coz the bronchial circulation is not

that enough .

so once there is obstruction of the small end arteriolar pulmonary

branches (which means that there is no blood supply for this area at the

part of this artery so it`s that last artery that supplies the area or the

only one )so once there is obstruction there will be no other blood

supply so this will lead to infarction.

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Recurrent emboli may cause pulmonary hypertension with right

ventricular failure. Now we said that the pulmonary artery originates

from the right ventricle so if the pulmonary vasculature faces suffered

from obstruction this will increase the blood pressure because there

will be more resistance so the heart will try to pump against the high

pressure , the embolism once it becomes in the Venus it becomes

fibrotic so this will minimize the size of the pulmonary circulation which

will lead to more resistance to the pumping heart .

So any right side heart failure secondary to the increase in the

pulmonary blood pressure or pulmonary causes is called cor

pulmonary or corpulmonale

SaddlePulmonary Thromboembolus

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We said that once the embolus is large we call it a saddle embolus . this

photo here represents the left pulmonary artery and the right

pulmonary artery , the heart is removed , so what`s left is the pulmonary

trunk so this thrombus or embolus it presents in this area and it`s

called the saddle embolus and it`s fatal . usually the source is the deep

vein thrombosis above the knee.

Microscopic appearanceofa pulmonary embolusinamajor

pulmonary artery branch

This section is from the lung parenchyma , all these things are the

alveolar and this is pulmonary artery or pulmonary branch and this is a

thrombus within the artery and this is a thrombus within the artery so

, the paleZahnThese lines are cold lines of.thrombo embolusthis is a

area is the platlets , the red area represents accumulation of RBC`s

within this part

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Systemic Thromboembolism: Emboliinarterial circulation

We talked about the pulmonary thromboembolism usually it`s source is

venous usually from the deep veins of the lower limb or the pelvis. once

there is arterial thromboembolism or emboli originating from the heartor the aorta the embolism in this case called a systemic embolism.

Etiology

80% cardiac mural thrombi and the development of these

thrombi is associated with * left ventricular wall infarction

And * dilated atria ( mitral valve disease)

Aortic aneurysms, thrombi on ulcerated atherosclerotic plaques,

fragmentation of valvular vegetations or paradoxical emboli

Paradoxical emboli : Venus originated embolus

( which means that once there is a defect in the inter atrial septum

"atrial septal defect" or open foramen or valve what will happen

to the venous thrombus is that sometimes it will go to the right

ventricle , it will cross the septum through this defect to the left

ventricle and then to the aorta and then to the systemic

circulation so instead of going to the pulmonary circulation it will

go to the systemic circulation)

Effectedsites : Depends on the site of origin :

o Lower limbs (75%)

o brain (10%)

o intestines, kidneys, and spleen

because these 3 organs have good boold supply .

consequences: infarction which will follow secondary by destruction

in the blood flow

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theinfarction depends on :

caliber ofoccluded vessels

if the caliber is big > it's occluded > then will lead to mass infarction

vulnerability toischemia

The brain for example can live without blood for 2 or 3 mins , And once

there is no establish for the circulation the brain will go infracted (

liqufactive type )

The infarction here due to ( ischemia )

The heart can tolerate ischemic conditions for 30 mins , whilefibroblasts can live for many hours .

collateral circulation

(collateral circulation that carried on through secondary

channels after obstruction of the principal channel supplying the

part.)

for example : if the main blood supply ( main artery ) is open ( no

stenosis ) ( low pressure) the blood will flow easily in it's pathway

through arteries and small arteries or arterioles which support the

circulation without needing for this collateral circulation but in

ischemic heart disease there is stenosis of one of the coronary

arteries , the pressure in the area before stenosis will increase so the

blood will try to go over this stenosis via other way ( collateral

circulation )

P.S : the older people usually have good sort of collateral circulation .

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Fat Embolism

Etiology:

Microscopic fat globules enter the circulation and get stuck in

somewhere ,

y mainly it's due to Any fractures in Long Bone ( femur ) in car

accident for example , and this may associated with Bone marrow

( or without)

y Soft tissue trauma.

This type of embolism occurs in most severe skeletal injuries ( 90%)

but only (10 %) show clinical manifestations , and the symptoms

usually appears within three days after injury .

The symptoms of Fat embolism is Known as Fat embolism Syndrome

and these symptoms sort as:

secondary pulmonary insufficiency :

Tachypnea ( increase in breath Rate ) .

Dyspnea .

Tachycardia .

Neurologic symptoms( less commonly )

Irritability restlessness

Alternation in consciousness

Anemia .

Thrombocytopenia.

10% fatal

Mechanism :Mechanical obstruction like thrombus embolism and

biochemical Injury due to fatty acids release in the site of obstruction.

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Air Embolism

100 mls of gas needed to cause this syndrome

Etiology

y Chest wall injury ( Air escape from lungs to the arteries or veins )

y Obstetric procedures

y Blood transfusion

y During hemodialysis for renal failure

y Injures and operations in head and neak

y Decompression sickness this happens in :

individuals are exposed to sudden changes in

atmospheric pressure , like : Scuba and Deep divers and

underwater construction workers ( building bridge forexample)

The high pressure in Deep sea compresses the Gas and convert it into

fluid state and once there is sudden decreasing in the pressure the fluid

will transform to gaseous state again and the same happens in our

body

At high pressure, nitrogen is dissolved in the plasma and in interstitialtissue, especially adipose tissue.

Return to normal atmospheric pressure, the gas comes out of solution

and small bubbles are formed within the interstitial tissues and blood.

Gas Emboli Lead to Ischemia in variety tissue .

Treatment : by putting the patient in high compressive area for a

while and then reduce the compression slowly ( slow decompression)

>> gradually transforming of the fluid into gas so body can deal with

amount of gas .

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Amniotic fluid Embolism

Amniotic fluid is the fluid surrounding the fetus in the pregnant lady,

sometimes during delivery this fluid might enter the maternal

circulation it`s rare but carries 20-40% mortality rate.

Manifestations are:

Respiratory failure (sudden severe dyspnea, cyanosis, and hypotensive

shock), seizures, and coma.

Now if the lady survives the crisis she shows pulmonary edema, and DIC

(discriminated intravascular coagulation) , which is secondary to therelease of thrombogenic substances from amniotic fluid.

if we took a section of the lung after death in the case of embolism we

expect to find squamous cells or hair within the blood vessel cause this

is what the amniotic fluid contain , so the presence of the squamous cells

in the blood vessel is an indicating factor that there is embolism.

Infarction

So the infarction is a result of thromboembolism and simply an ischemic

necrosis caused by occlusion of either arterial supply or the venous

drainage of a particular tissue. 99% are caused by arterial occlusion due

to thrombotic or thromboembolic events.

Less common causesinclude:

Vasospasm

Expansion of an atheroma due to intra-plaque hemorrhage*

*Twisted vessel (testicular torsion or volvulus)

Vascular compression by edema, or tumor.*


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Not all heart attacks are secondary to thrombosis , it might be sort of

vasospasm of the coronary artery this will lead to the symptoms of

ischemia so if we do catheterization we will find normal cadaver bloodvessels but the mechanism is due to vasospasm.

The twisted vessels: testicular torsion if the testes torted along it`s long

axis or the spermatic cord which usually contains veins and arteries, but

once there is a twist it`s easier to block the vein drainage but the arterial

supply will stay on. So once there is a blockage for the venous

circulation this will produce sort of congestion which will increase the

pressure and sometimes it will lead to decrease of the arterial supply to

the tissue which will lead to infarction. So the examples are testiculartorsion or volvulus which is the twisting of the intestine around it`s

middle.

Infarct Morphology

All infarcts tend to be wedge-shaped, the occluded vessel marks the

apex, and the organ periphery forms the base. Lateral margins may beirregular reflecting the pattern of adjacent vascular supply , sometimes

the boundaries of the infarction is not that obvious because the tissue

will have blood from other sources.

An infarct swells, and often protrudes above the surface of the organ.

However the chronic infarction the infarction can be rephrased by the

fibrosis is sort of shaking to the tissue so after while this infarction will

shrink under the surface of the organ.

A fresh infarct is pale because of the loss of red blood cells, an

appearance reflected in the terms white or pale infarct. Infarcts can

also be red (hemorrhagic), particularly in the lung and the intestine.

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With time, the tissue surrounding an infarct forms granulation tissue

rich in capillaries that bleed easily. Therefore, the border of a healing

infarct is frequently hemorrhagic.

Typesofinfarction :

1.Red infarcts (hemorrhagic) vs White infarcts (anemic)

2.Septic infarcts (occur with embolization of infected cardiac

vegetations or when microbes seed an area of necrosis) vsbland(when

there is no infection).

Redand White Infarcts

Red Infarctsoccur:

In venous occlusion (ovarian torsion)

In loose tissues (lungs, placenta)

In tissues with dual circulation (lungs and small intestine).

In tissues previously congested because of sluggish venous

outflow.

At site of previous occlusion and necrosis when flow is re-

established.Whiteinfarctsoccur :

in solid organs (heart, spleen and kidney, with end arterial circulation).

Factorsinfluencing thedevelopmentofaninfarct

Nature of vascular supply

1)Organs with dual circulation (lung, liver) protected against

infarction

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2)Organs supplied with end arteries (spleen, kidneys) usually

develop infarct after occlusion of their arterial supply.

Rate of the development of arterial occlusion:

Slowly developing occlusions less often cause infarction by providingtime to develop alternative perfusion pathways (collaterals).

If there is sudden occlusion this will lead to infarction while if the

occlusion is partially or slowly this will give time to the tissue to

produce collaterals and save the tissue from infarction .

Neurons, brain, heart, fibroblast as we said have the capabilitie to

withstand ischemia ,and also depends on the blood oxygen content , and

if there is already anemia or heart failure any alteration in the blood

flow may lead to infarction , because this is already ischemic secondary

to anemia or secondary to heart failure .

SHOCK

Now to the last subject which is the shock its the last common pathway

for a number of potentially related events including severe hemorrhage

so severe bleeding will lead to development of what we call

hypovolemic shock ,extensive trauma ,myocardial infarction, massive

pulmonary embolism ,microbial sepsis, trauma to the spinal cord or

hypersensitivity reactions that leads to what we call anaphylactic shock.

The definition of shock a systemic hypo perfusion due to either reduced

cardiac output or reduced effective circulatory blood volume this will

lead to hypotension ,impaired tissue perfusion , cellular hypoxia this

will lead to cellular injury and if severe will lead to tissue necrosis which

is irreversible .

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Typesofshocks:

1- cardiogenic shock: due to problem in the heart , so the heart will

be unable to pump more blood ,this happens due to myocardial

infarction , can happen secondary to heart arrhythmia especiallyventricular ones ( ventricular arrhythmia ) ,extrinsic compression like

cardiac tamponade which means bleeding in the pericardial space once

there is blood in the pericardial space this leads to increase in the

pressure in this space this will alter or decrease the ability of the heart

to pump also obstruction like pulmonary embolism leads to cardiogenic

shock .

SAMA ( cardiac tamponade : when the space between the epi- and the

peri-cardium is filled with blood or any fluid usually due to trauma and

outflow obstruction like pulmonary embolism ).

2- hypovolemic shock : is very simple ,once there is massive blood

loss this will lead to decrease in the effective blood volume .and its

usually caused by hemorrhage ,vomiting , diarria or extensive burns and

trauma

3- septic shock :this is caused my microbial infection and usually the

main cause is gram negative bacteria ,and the endotoxins produced by

these gram negative bacteria ,so the other name for septic shock is

endotoxic shock .

4 -spinal shock : if there is trauma in the spinal cord and it's severe

trauma ,this could lead to sudden death without any explanation

,usually the explanation is what is called neurogenic shock .

5- anaphylactic shock : hypersensitivity shock usually mediated by

the mast cells or IgE ( IMMUNOGLOBULIN E ) .

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Now we will discuss this Topic as discussed in the book

Septicshock

-Septic shock it carries high mortality rate ( 25-50%) depends on the

hospital or where the patient is usually it results from the innate

immune response to infectious agents rather than the infection itself ,

infectious agents might be blood borne( the bacteria is in the blood or

might be secondary to adjacent organ or tissue that would be the source

of the bacteria ) .

As I said before 70% of septic shocks are caused by endotoxin

producing gram negative bacteria , endotoxins are bacterial wall

lipopolysaccharides or LPS.

The LPS is composed of toxic fatty acid core ( lipid A) and surrounded

by a polysaccharide coat (O antigen ) .

The fatty acid core is similar to all bacterial organism however the

polysaccharide is different depending on the bacteria type .

LPS as a complex binds to a circulating LPS binding protein this is

circulating in the blood this complex is able to bind to what we call the

CD14 receptor on the inflammatory cells : monocytes ,macrophages and

neutrophils.

Once there is binding to the LPS-CD14 there is what is called the TLR-4

associated protein this is adjacent to the CD14 receptor ,once there is

activation to this TLR-4 this will lead to production to what we call the

TNF AND IL-1 ( tumor necrosis factor and interleukin -1) this will to

acascade and production of IL-6 AND IL-8 this will lead to production of

nitric oxide and platelet activating factor and other mediators and allthese mediators will lead to the consequences or the causes of the

symptoms of the shock .

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So the severity of the shock depends on what ? on the concentration of

these mediator -if these mediators are in low doses this will lead to local

inflammation

-if in medial doses will lead to minor systemic effects like fever or acutephase reactants increase in blood

-if in high doses it will lead to development of the shock.

LPS-CD14-TLR-4

TNF & IL-1

IL-6/IL-8

NO, PAF

other mediators

Low doses

Monocyte activation

Enothelial activation

Complement activation

Local inflammation

Medium doses

Fever

Acute phase

reactants

Systemic effects

High doses

Systemic vasodilatation

Deacreased myocardial

contractility

Endothelial injury:

thrombosis, DIC

ARDS

Septic shock

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Themechanism as wejustdiscussedanditsdetailsfromslides :

With severe infection: High LPS causes high level of secretion of

cytokines and secondary mediators causing:

Systemic vasodilation (hypotension)

Decreased myocardial contractibility.

Widespread endocardial injury and activation with systemic

leukocyte adhesion and pulmonary alveolar capillary

damage (adult respiratory distress syndrome-ARDS).

Activation of the coagulation system causes disseminated

intravascular coagulation.

Stagesofshock

Non-progressive stage:

Compensatory mechanisms maintains perfusion of vital organs.

Progressive stage:

Tissue hypoperfusion with metabolic and worsening circulatory

imbalances.

Irreversible stage:

Severe irreversible tissue and cellular injury.

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Compensatory Mechanisms in Shock

Baroreceptor reflexes.

Release of catecholamines.

Renin-angiotensin-aldosterone system.

ADH release.

Generalized sympathetic stimulation.

Net effects:

Tachycardia.

Fluid retention.Peripheral vasoconstriction.

THE HAPPY END

elle sa3dtna wZainah MataniShokran jazellaan la a7ala

a3tatna mn w2t-ha el 3'ali b heak fatra 7arejeh

#26 ,, script patho ,, systemic thromboembolism

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