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Ala'a khubazan Pathology-sheet #1531-OCT-2013

>>In this lecture we are going to talk about Aneurysms & its types, for each type we will talk about (pathogenesis, morphology and clinical application) we

will take it one by one in details .

- Aneurysm: is an abnormal dilation of blood vessel or heart, particularly it affects major (large) blood vessels, can be divided into:

1-" true" aneurysm :- the dilated part of blood vessel should contain the vessel wall with its 3 layers (intima , media, and adventitia) that means that

this dilation involves the vessel wall in full thickness and that's why it's true .

2- “false” aneurysm :- also known as (pseudo –aneurysm ) .

- These actually are not an aneurysm because this aneurysm is result from leakage of blood into outside the blood vessel, however this clot or local bleeding it's localized by some connective tissue so stay in its place within outer surface of blood vessel, however if you look grossly at blood vessels involves this false aneurysm will be exactly as appearance of true aneurysms (which appears dilated just like true one).

-false aneurysms lack the vessel wall , because considered as rupture or damage , so there is rupture or damage that leads to exit blood outside .

- This hematoma or clot that produced by this false aneurysm, freely communicates with the intravascular space and show pulsating movement. Although this hematoma is not blood vessel but its connection with intravascular space make them pulsating and that's why we called them (pulsating hematoma).

-One of Examples for this type of aneurysms : aneurysms that results from rupture of ventricles after MI ( this rupture occurs after necrosis and infraction ) , however this can't extend outside because surrounded by pericardium so it stills localized in this area , so this can appear as local enlargement similar to that of true aneurysm .

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** Arterial dissection:

Can occur aneurysm due to dissection and known as "Dissected aneurysms" .

-Dissection means: some of blood enters the blood vessel wall and dissecting through the layers and separate them from each other , this can create some of enlargement in thickness of blood vessel wall and enlarment in blood vessel wall in general .

-the blood that dissects among blood vessel layers can cause damage and necrosis to vascular wall and this make the area of dissection is very weak . So if this blood to any reason expose to any pressure (increase in blood pressure) this weak area will rupture and this can lead to death of patient.

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** Aneurysms are classified also by macroscopic shape and size into:

1- Saccular aneurysms : -Weakness of blood vessel wall involve focal area of blood vessels , this result a dilation in this weak area and eventually will be formed a spherical out pouch through the blood vessel.

-importance of this type , this pouches are connected to blood so its flow will be abnormal and be very slow , this will result a stagnation in flow , this stagnation always be cause to initiate the thrombosis , so at end this aneurysms can lead to thrombosis .

2- Fusiform aneurysms :

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-considered as aneurysms that involve whole circumference ( the whole weak wall ) , these aneurysms can vary in length and diameter ( depending on the site of these aneurysms ) . - any blood can be affected by this type , but actually there are common sites that involve this type as : ( 1- aortic arch 2- abdominal aorta 3- branches of abdominal aorta like iliac arteries .

-this type of aneurysm can be serious and can lead to death and this absolutely depend on site of aneurysms.

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** Aortic aneurysms:

Aorta is a famous site for different types of aneurysms and the causes that lead to this are:

1-atherosclerosis: most common cause, atherosclerosis results from deposition of fatty material within the blood vessel wall, and this associated with weakness of this wall and at end will be dilation in this blood vessel.

2- cystic medial degeneration of the arterial media :-Some of media can be lost and degenerated; this will lead to gaps within this area which can cause weakness of wall.

-This can be produced from inherited and acquired reasons: **inherited (genetic) reasons : as congenital defects ( known as berry aneurysms which commonly occurs in vessels of brain ) .

**acquired reasons : 1- infections (like mycotic aneurysms) 2- systemic diseases 3- direct trauma to vessels so will lead to

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degeneration and weakness of wall which can produce aneurysms later on .

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**mycotic aneurysms: -is an aneurysm that exist in large blood vessel and its occurrence associates with infectious agents reasons. -Is one form of aneurysms which caused by infection.- This aneurysm not caused by fungal infection but caused by infectious agent in general (unnecessarily to be caused by mycotic fungal infection) . -this inflammation process of blood vessel by infectious agents leads to weakness of the wall of blood vessel and production of aneurysms.

**complications: 1- Thrombosis: this dilation in blood vessel can lead to stagnation which produces thrombi. 2- Rupture __________________** Those microorganism that lead to this type of aneurysm can originate from:

1- embolization of a septic thrombus : ( as we said before in previous lectures that the fate of embolism that can be superimposed infection in this embolus , ( so these emboli can formed later on superimposed infection produced in this embolus ) , very important example is (infective endocarditis : it's an inflammation of endocardium ( which is the lining of the heart ) , occurrence of endocarditis mostly due to microorganism and this microorganism can travel through blood and reaches major blood vessels .

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2- Extension of an adjacent suppurative process: bacteria source from adjacent infection, which means if we have an abscess in area (for e.g. ( around aorta ) so can occur extension of this to another place (for lung as an example ).

3- Circulating organisms directly infecting the arterial wall: the microorganism can be part of septicemia and reach the blood wall directly.

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**Mycotic abdominal aortic aneurysms:

-is very common one because the GI tract is rich of different microorganism so it can lead to different types of infections in GI tract , and this microorganism can reach the aorta .

- Most common cause of this is : ( Salmonella gastroenteritis ) ( here we get infection by salmonelaa then followed by gastroenteritis ) .

- This salmonella can extend and this extension always associated with weakening and rupture of blood vessel wall.

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A- normal vessel : it's almost same distance from the beginning to the end , then this vessel can start to branch and this branches will be smaller than the original vessel .

B- True aneurysm ( saccular ) : called True –because this involves the 3 layers & called sacuular -because don't involve whole circumference but just a certain focal area .

C- True fusiform : called True –because this involves the 3 layers & called Fusiform –because involve the whole circumference and appears just like barrel shape .

D- False aneurysm : although it's not an aneurysm but it's appearance similar to it , it's just a leakage of blood or localized hematoma ( hematoma just around blood vessel and don’t move to anyplace , stay in its place due to presence of some connective tissue around it so this hematoma still connected with lumen )

E- Dissected aneurysm: because of hematoma is connected with lumen so can be damage to endothelium and this allow to little (just little amount ) blood to enter to blood vessel wall so blood dissected and this give us Dissected aneurysm .

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**Note : all of these aneurysm associate with weakness of the wall , so rupture always is a major consequence of the aneurysms .

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** Abdomial aortic anuerysm :

- abdominal aorta is a common site to have aneurysm

- most common cause of this anurysm is : atherosclerosis that can involve different arteries not just abdominal artery but can also involve (iliac artery, arch of aorta and descending parts of thoracic aorta ) all of these can involve but the most site is abdominal aorta .

** Pathogenesis:

1- Atherosclerosis (most common cause ) . The age that we expect to see Abdomial aortic anuerysm is the same age of atherosclerosis which is at middle age and above (50 years old and above ) .

2-Hereditary defects in structural components of aorta : defect in collagen synthesis , there is inherited condition that involves defect in gene which responsible for synthesis of collagen ( particularly fibrillin )

-Marfan syndrome has relation with defect of fibriliin so those patients are unable to produce collagen . ( collagen normally composed from 4 chains ( 2 alpha + 2 beta ) , abnormality in one component is associated with weakness of all collagen fiber )

- because collagen is present at different sites , Marfan syndrome has different magnifications , so Marfan syndrome not only affect the cardiovascular system ( however it's one of most dangerous sites )

Continue to pathogenesis to Marfan syndrome particularly:

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1-collagen defective means that wall is abnormal & it's not as should be , collagen will be soft and doesn't give the strength which needed in the large vessel so vessel will is going to be softer than the normal .

2- Macrophage also involved and unable to produce as normal .

3-Decreased level of tissue inhibitor of metalloproteinases ( which consider as group of enzymes that involve in collagen degradation ) (TIMP) , if there is chemical that decrease the inhibition of metalloproteinases so these enzymes will be powerful and associated with more destruction than should be and this can affect the vessels .

**Morphology of abdominal aortic aneurysms :

1- Usually positioned below the renal arteries and above the bifurcation of the aorta

2- Can be saccular or fusiform

3- Can be as large as 15 cm in diameter (as 3 times than normal vessel ), and as long as 25 cm ( it means that can involve the entire length of artery and not just localized , this indicates that aneurysm can be very large and this associated with more complication )

4- Microscopically: atherosclerosis with destruction and thinning of the underlying aortic media

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**Inflammatory abdominal aortic aneurysm :

-This type is associated with inflammation, so if we look to this vessel we can predict what the underlying cause of the inflammation is .

-because this type is due to inflammation so the signs of inflammatory process exist here , and in addition there is infiltration of inflammatory cells within vessel wall not just around it be inside it as well .

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**Syphilitic aneurysms:

- it happens due to syphilis infection ( now a days this infection can be treated in early stages , that's why advance ( tertiary ) stage is uncommon , and these type of aneurysm happen at advance stage so that's why it's very rare to found this type now a days .

- Caused by The spirochetes T. pallidum (it's a bacteria that cause syphilis infection)

- syphilis not only can affect large blood vessel but also the small blood vessel and this case known as obliterative endarteritis ( the blood vessels that involves in this process are the blood vessels that supplying the major blood vessel ( especially the blood vessel with thick wall needed more blood so it supplies by the small blood vessels , but the small blood vessels because there thickness is less so there are supplied usually by diffusion .

- those small blood vessels which supplies the major one known as vasa vasorum , vasa vasorum of the aorta can be involved in syphilitic infection and this infection can obstruct this vasa vasorum and when occur obstruction to this will lead to degeneration and necrosis and this produce aneurysms .

- if Syphilitic aneurysms occurred in the heart valves , this will cause valve stenosis , and this stenosis after a long period of time lead to dilation of the heart , so heart be very large in size (hypertrophy) , this known as (cor bovinum" (cow's heart).

>>>>In slide # 16 , you can see in abdominal aortic anueysms that this blood vessel in upper side and lower one is normal but in middle is dilated and there is a clot ( always the dilated region there is a clot in it ) , the clot formed because the flow slow down in this area so the clot is formed .

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**The clinical consequences of abdominal aortic aneurysm (complications):

1- Rupture (this is not just for abdominal aortic aneurysm but also for other aneurysms): rupture means that there is sudden loss of large volume of blood which can create cardiac shock so the patient can die rapidly >> this is really a very serious and critical condition.

- if someone we diagnose him that he has aneurysm , the mortality risk is about 5% , but if you try to treat the aneurysm the mortality risk will increase to 50% , this is due to the possibility of occurrence of rupture which is fetal so the risk of mortality will increase .

- It's very critical to choose leave aneurysm or not, both of them are critical and dangerous and can be fetal to patient as well.

2- Obstruction : if the artery is dilated , it can compress the vessels ( branching vessels ) , when there is compression so there is ischemia to organs that supply by theses arteries and its branches , (this obstruction can be dangerous or not , this depend on level of compression ( complete or partial ) , and the site of compression ) .

- This compression can be in :

1- Iliac artery >> lead to leg infraction

2- Renal artery >>lead to kidney infraction

3- Mesenteric artery >> lead to GI infraction

4- Vertebral artery >> lead to spinal cord infraction

3- Embolism: as result of aneurysm can be formed thrombus , this thrombus can lead to emboli and this will form another infraction .

4- Impingement and compression on an adjacent structure : for example : compression in ureter can lead to failure or infraction in kidney .

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5- abdominal aneurysm : this can diagnosed as tumors or masses , but those masses can pulsate because those abdominal aneurysm considered as connection of blood vessels so it must have a pulse , but the masses or tumors there is no pulse in it , so by the pulse we can differentiate between tumors and abdominal aneurysm .

Slide #28 >> this slide show you how aortic dissection appears , as we said the dissection is entry of blood inside blood vessel wall .

In B – you can see that blood not in lumen but within the wall , we notice that the thickness of the wall increases because of presence of blood . Note : the start in the pic indicates the RBCs inside the wall of blood vessels .

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**Aortic dissection :

-Should be some sort of injury that allow blood to leave lumen and enter to blood vessel wall.

-The aortic dissection is a very serious and critical condition and this refer to its complications which are:

1- Massive hemorrhage within blood vessel wall .

2- Cardiac tamponade ( very serious condition ) : after dissection the vessel wall get weaken and this associated with extension of blood into the outside area and this can occur especially in the heart that known as " cardiac tamponade " , which means that there is destruction of cardiac wall then blood start to go out from the heart into pericardium and accumulate here .

-the heart to be able to contract must be surrounded by free space , in cardiac temponade , the cardiac contraction can be prevented because the free space is full of blood so this contraction not be normal anymore and this results in sudden failure in the heart , so cardiac tamponade can be fetal .

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**pathogenesis (causes of aortic dissection) :

1- hypertension ( most common cause ) : As we said must be some sort of injury in endothelial to allow blood to enter the wall , so endothelial under increase of pressure can cause injury .

2-inherited or acquired connective tissue disorders causing abnormal vascular ECM:

** inherited diseases such as : ( 1- Marfan syndrome ( we will talk about it later in this sheet )

2- Ehlers-Danlos syndrome

** acquired diseases : 1- vitamin c deficiency : vitamin c is very important for collagen synthesis and that's why if it's deficient this will affect on synthesis of collagen ( because one of a.a in collagen can’t synthesized without presence Vitamin C) , so all the organs that contain collagen will suffer and one of them is the vessel .

2- copper metabolic defects ( any presence of toxic can affect the vessels )

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** Marfan syndrome:

- due to that collagen exist in different places , so this syndrome affect other places in addition to cardiovascular , Marfan syndrome can affect also :

1-Skeletal muscle and lead to Skeletal abnormalities this occur because the bone actually they have a good amount of collagen, so if collagen is abnormal the bone will be soft.

2-lens: the lens has many collagens, so any abnormality in collagen will lead to ocular abnormality.

**Aortic dissections are classified generally into two types :

** Aorta is the common site that can be affected by many sorts of aneurysms , so it's important to be classified depending to severity to predict to outcome .

- DeBakey calcification:

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- DeBakey classify aortic dissection into 3 types (I , II , III )

I: is aortic dissection that involves ascending aorta only.

II: is aortic dissection that involve both ascending and descending.

III: is aortic dissection that involve just distal to subclavian artery .

, but now a days, some modifications occur and re-classify it to ( A & B) .

- DeBakey I and II >> type A

-DeBakey III >> type B

* NOTE : The more dangerous is type A , because involve the ascending part of aorta ( it ascends from the heart so the heart can be involved by this process )

** NOTE: I and II >> is much difficult to treat than type III , because type III is away from the major vessels which is subclavian artery and just distal to it .

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** Clinical course:

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- Aneurysm is very serious, if you treat it or leave it both of them is serious.

- In old days this aneurysm was very dangerous and lead to death, but now a days is better( Rapid diagnosis and institution of intensive antihypertensive therapy, coupled with surgical procedures involving plication of the aorta) but still there is some dangerous , but survival rate of patient with aneurysm be up and up to about 65-75 % and this actually very good percentage .

THE END

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