Path Lecture 40-41: Blood Vessel Pathology

Arterial Aneurysms & Dissections
10/22/13 9:10 PM
Blood Vessel Structure
x Tunica Intima
o Innermost layer composed of endothelial cells and
subendothelial matrix
x Tunica Media
o Smooth muscle, elastic fibers
o Internal elastic lamina separates the media and intima
o External elastic lamina separates the media and the
adventitia
x Tunica Adventitia
o Longitudinal ECM fibers
o Contains vasa vasorum
ƒ Blood vessels that supply blood to the cells of the
arteries

Types of Arteries
x Large – Elastic Fibers
o Allow for expansion and recoil
x Medium – Muscular Fibers (Smooth muscle cells)
o Vasoconstriction & dilation
x Small Arteries/Arterioles
o Increased resistance
o Decreased speed

o Allows for gas exchange in capillaries
Vascular Disease
x Cardiovascular disease is the leading cause of morbidity and
mortality in adults
x Pathology of vessel disorders can be divided into 2 categories
o Narrowing of Vessel Lumen
ƒ Leads to obstruction
ƒ Slow Stenosis
à Arteriosclerosis
ƒ Acute stenosis
à Thrombosis/embolism
o Weakening of the Vessel Wall
ƒ Leads to dilation and rupture
ƒ Aneurysm
à Localized, abnormal dilation of a blood vessel
à Makes vessel unable to recoil properly
ƒ Dissection
à Tear within a vessel wall
Aneurysm Classification
x Morphology – False vs. True
x Location – Aortic (abdominal, thoracic), Intracranial
x Etiology
Morphology
x True Aneurysms
o Arterial wall is intact, but attenuated Æ vascular dilation
ƒ Atherosclerotic, syphilitic, and congenital aneurysms
o Saccular, Fusiform
x False Aneurysms
o Breaks in arterial wall cause hematoma that communicates
with the intravascular space
ƒ Pulsating meatoma
ƒ Leaks at anastomoses 

Location
Aortic
x Divided into thoracic aortic aneurysms, and abdominal aortic
aneurysms
x Most important predisposing factors
o Atherosclerosis Æ AAA
o Hypertension Æ Thoracic (Ascending)
o Marfan’s Syndrome Æ AAA or thoracic
ƒ FBN1 mutation that affects microfibrils
ƒ Leads to poor elastin formation in tunica media
ƒ Leads to other problems such as lens dislocation,
curvature of spine, funnel chest, lung collapse
x Mechanisms of Aneurysm Formation
o Defect in vessel wall integrity
ƒ Loeys-Dietz Aortic Aneurysm
à TGF-ß gene mutation (similar to Marfan)

weakening of vessel wall à Inflammation also reduces TIMP expression. enhancing MMP action o Cystic medial degeneration ƒ Relates to events leading to smooth muscle loss ƒ Fibrous deposition and degeneration of vessel wall media ƒ Often ischemic ƒ Atherosclerosis and hypertensions ƒ Shown below is elastin stain with * marking where degeneration of elastic tissue has occurred  ƒ x o Trauma o Anatomic Malformations o Vasculitis o Infections o Tertiary Syphilis Thoracic o Less common than AAA o Etiology ƒ Hypertension is the most common risk factor .Ehlers-Danlos Syndrome à Collage types I and III defect ƒ Vitamin C Deficiency à Altered collagen cross-linking o Proteolytic degradation of vessel wall ƒ MMP à Inflammation recruits cells that release MMPs à Degradation of vessel walls.

buttocks. irreversible arterial dilation due to destruction of the vessel wall by infection à Can arise from: x Septic emboli (endocarditis) x Bacteremic seeding / inoculation o Salmonella gastroenteritis x Contiguous infection o Signs/Symptoms ƒ Asymptomatic ƒ If symptoms are present à Abdominal discomfort à Can spread to groin. smokers. legs & flanks ƒ Pulsating sensation/mass in abdomen o Clinical Complications ƒ Rupture à Results in massive hemorrhage and hypotension à Risk related to size x Aneurysms >5cm are managed aggressively by surgical bypass x Involves prosthetic grafts or endoluminal stentss à Hypotensive shock . >60 years old o Etiologic Factors ƒ Atherosclerosis is the most common cause ƒ Marfan Syndrome (weakens vessel wall) o Sites of Involvement ƒ Infrarenal (90%) – Just below renal arteries ƒ Pararenal ƒ Suprarenal o Two important variants ƒ Inflammatory à Results from idiopathic periaortic fibrosis and inflammation à Inflammation weakens the vessel wall ƒ Mycotic à Localized.ƒ o Sites ƒ ƒ ƒ x Marfan syndrome (weakens vessel wall) of Involvement Ascending – 40-50% Aortic Arch – 10% Descending – 45-50% Abomdinal Aortic Aneurysm (AAA) o High risk groups ƒ Men.

altered mental status.x Cyanosis. drugs  Aortic Dissection x Accumulation of blood between layers of the blood vessels (tunica media) via tears in the tunica lamina . vasculitis. mottling. tachycardia ƒ Obstruction à Ischemic injury of downstream tissues ƒ Embolism à From atheroma or mural thrombus ƒ Compression à Of adjacent structures Intracranial (Berry Aneurysms) x Most common kind of aneurysm in the brain x Results from anatomic/congenital malformation o Focal attenuation of tunica media and elastic lamina x Sites of involvement o Major bifurcations in Circle of Willis o Most commonly occurs in the anterior communicating artery bifurcation x Sequelae o Rupture/subarachnoid hemorrhage (90% risk of death) o Aggravated by hypertension ƒ Renal disease.

bypass surgery Pathogenesis o Hypertension is the major risk factor ƒ Due to cystic medial degeneration o Intimal tear allows blood flow to dissect through the media and travel along the aorta distally .x x x x Most common to 40-60 year old men with hyptertension Also in younger patients with CT diseases Some are iatrogenic o Diagnostic catheter.

o Most common site is the ascending aorta    x   Classification of Aortic Dissections o DeBakey Types ƒ I – Ascending and descending ƒ II – Ascending only ƒ III – Descending only o Stanford Classifications ƒ A – All dissections involving ascending aorta. regardless of site of origin .

stabbing ƒ Radiates to the neck or down the back o Loss of Consciousness o Different pulse rates in each arm (if it affects the arch) o Shortness of breath o Weakness/paralysis o Sweating Clinical Complications / Sequelae o Rupture ƒ Most common cause of death . ripping.ƒ x x B – All dissections NOT involving ascending aorta  Clinical Symptoms o Sudden severe chest / upper back pain ƒ Described as tearing.

ƒ Pericardial tamponade may occur if rupture is .

proximal to the heart  .

o Retrgrade Extension (Proximal) ƒ Aortic valve insufficiency ƒ Myocardial Infarction  o Anterograde Extension (Distal) ƒ Compression of aortic branches obstructing flow to distal organs .

.

congestion.Varicose Veins x Abnormally dilated. superficial veins of the lower extremities x Vascular dilation results from high intraluminal pressure and loss of structural support x Increased venous pressure can be caused by o Obesity o Pregnancy ƒ Vena cava compressed by fetus o After prolonged periods of standing x Varicose dilation leads to incompetent venous valves o Leads to stasis. pain. and thrombosis x Clinical Symptoms o Stasis dermatitis & ulcerations o Poor wound healing o Superimposed infections o Embolism from superficial veins is very rare Portal Hypertension & Varices x Increased portal pressure due to o Cirrhosis o Portal vein obstruction o Hepatic vein thrombosis x Leads to development of o Porto-systemic collateral vessels (Shunts) x Collateral vessels become prominent and dilated . tortuous. edema.

o Gastroesophageal veins o Umbilical veins o Hemorrhoidal veins  x Esophageal Varices o Responsible for the main complications of portal hypertension ƒ Massive upper GI hemorrhage and bleeding with rupture  .

o Caput Medusa ƒ Distended and engorged periumbilical veins radiating across the abdominal wall o Hemorrhoids ƒ Dilation of anal veins .

ƒ ƒ Internal or external depending on location relative to dentate line Caused by à Straining. Constipation à Sitting for long periods of time à Anal infections à Cirrhosis Superior Vena Cava Syndrome x Compression of superior vena cava results in venous flow obstruction x Clinical complications o Dilation of head. or lower extremity vein thrombi x IVC causes: o Lower extremity edema o Distension of the superficial collateral veins of lower abdomen o Renal dysfunction Deep Vein Thrombosis x DVT is 3rd most common CV condition after CAD and stroke x Virchow’s Triad o Stasis o Vessel wall injury o Hypercoagulability x Pulmonary embolism results form fragmentation of the venous thrombus and causes arterial obstruction Lymphangitis x Acute inflammation of lymphatic vessels secondary to spread of bacterial infection o Group A ß-hemolytic strep is the most common cause . & arm veins o Cyanosis o Dilation/compression of pulmonary vasculature ƒ Causes respiratory distress x Bronchigenic carcinoma and mediastinal lymphoma are the most common malignancies associated with SVCS Inferior Vena Cava Syndrome x Caused by malignancies that compress or invade the IVC x Most commonly cased by: o Hepatocellular carcinoma o Renal cell carcinoma o Also caused by extension from hepatic. neck. renal.

overlying skin becomes edematous. painful streaks along affected lymphatic paths o Painful enlargement of lymph nodes (acute lymphadenitis) Lymphedema x Increase in the lymphatic hydrostatic pressure due to flow obstruction x Primary Lymphedema o Congenital o Results form lymphatic agenesis or hypoplasia x Secondary Lymphedema o Blockage of normal lymphatics due to ƒ Malignant involvement ƒ Surgical procedures that remove regional groups of lymph nodes à Eg) Axiallary lymph nodes in radical mastectomy ƒ Post-irradiation fibrosis ƒ Filariasis ƒ Post-inflammatory thrombosis and scarring x With time. and ulcerated o Advaced cases can result in massive engorgement of the affected extremity ƒ Decrease / loss of function (lymphostatic elephantiasis)  . indurated.x x o Most commonly seen in children Bacteria usually contained in lymph nodes o Extension into venous circulation results in bacteremia or sepsis o Extension through vessel wall can produce cellulitis & focal abscesses Clinically o Red.

x x   Rupture of obstructed lymphatics can also lead to extensive lymph accumulations in body cavities Histosection shows replacement of lymph node tissue by canerous tissue Æ obstruction  .

Vasculitis x Inflammation of the vessel wall with deleterious consequences on downstream tissues x Diverse disease group categorized by etiology and size of vessel involved Most common etiologic mechanisms x Noninfetious o Immune-mediated inflammation x Infectious o Colonized by infectious pathogens x Physical/Chemical Injury o Irradiation. mechanical trauma. toxins x Distinction of etiology is important for management Noninfectious Vasculitis pathophyisologic mechanisms x Immune complex deposition o Circulating antigen-antibody complexes deposit in vascular beds and cause an inflammatory response o Can be associated with ƒ Autoimmune disorders à SLE ƒ Drug hypersensitivities à Penicillin ƒ Viral infections à HBV x Anti-neutrophil cytoplasmic antibodies o ANCAs ƒ Diverse group of autoantibodies directed against neutrophils. and endothelial cells ƒ Classified based on intracellular distribution and target antigens à Perinuclear (p-ANCA) x Anti-myeloperoxidase (MPO-ANCA) à Cytoplasmic (c-ANCA) x Anti-Proteinase-3 (PR3-ANCA) o ANCA titers are measured by ELISA studies . monocyte lysososmes.

Type is determined by indirect immunofluorescence Titers reflect degree of inflammatory activity and recurrence (clinical management) o ANCAs directly activate neutrophils ƒ Stimulates release of ROS and proteolytic enzymes ƒ Causes endothelial cell damage o Pathogenesis poorly understood ƒ ANCA production induced by cross-reactivity ƒ Predisposing inflammatory stimuli upregulate MPO/PR3 ƒ ƒ x x Anti-endothelial cell antibodies o Kawasaki’s Disease For most vasculitses a specific causative agent has not yet been defined o Therefore. site of involvement is an important clue in diagnosis Vessel Size Involvement .

granulomatous inflammation of: o Large vessels of the head ƒ Temporal. TNF. and humoral response o Anti-endothelial Ab x Morphologic Findings o Granulomatous inflammation of media o Intimal fibrosis . vertebral & ophthalmic arteries x Ophthalmic involvement o Can lead to permanent blindness x Sensitive to treatment with corticosteroids and anti-TNF in refractory cases o Prompt diagnosis is important! x Etiology Uncertain o T cell response against a vessel antigen o Release of cytokines.Giant Cell (Temporal) Arteritis x Most common form of vasculitis in the US x Affects adults >50y o Particularly the elderly x Chronic.

o Disruption of internal elastic lamina .

use AGE o <50y = Takayasu Aortitis o >50y= Giant cell Aortitis x Variable course (slow or rapid) x Diagnosis o Clinical findings o Elevated ESR x Treatment o Corticosteroids . fatigue. weight loss o Headaches o Facial Pain o Pain on palpation along the course of the superficial temporal artery o Ocular Symptoms ƒ Diplopia Æ vision loss Diagnosis o Clinical findings o Elevated ESR (erythrocyte sedimentation rate?) o Histiologic confirmation Takayasu Arteritis x Granulomatous vasculitis of the medium-large arteries and aorta o Almost targets the aorta ƒ Aortic Arch and great vessels (60%) ƒ Distal aorta and branches (30%) x To distinguish from giant cell arteritis.x x Clinical Features o Fever.

x Clincial Findings o Initial symptoms nonspecific o Progression leads to: ƒ Pulseless disease à Reduced BP and pulses in arms ƒ Ocular disturbances (visual defects. but 3 categories recognized o Idiopathic o Cutaneous o HBV associated ƒ Cross-reactivity with IC x Affects all ages. typically young adults x Variable clinical course o Episodic with long free intervals x Clinical findings o Peripheral ischemia in skin & nerves Æ neuritis o Hypertension (renal vessels) ƒ Renal failure – Major cause of death o Abdominal pain & melena ƒ From GI ischemia o Fatal if untreated – Usually during acute attack ƒ Quick progression ƒ Treatment based on corticosteroids and cyclophosphamide (anti-inflammatories) . GI x Pathogenesis unknown. retinal hemorrhages. liver. total blindness) ƒ Neurologic Deficits ƒ Pulmonary hypertension (pulmonary artery) ƒ Narrowing of coronary ostia à Can lead to MI ƒ Systemic hypertension (renal arteries) Polyarteritis Nodosa (PAN) x Segmental necrotizing transmural vasculitis x Small-medium sized arteries x Involves visceral vessels o Kidney. heart.

eosinophils. monocytes) o Fibrinoid necrosis & thrombosis  x Chronic Stage o Fibrous thickening (scarring) of vessel wall  .Acute Stage o Transmural inflammation (neutrophils.

x x Different stages can be seen in a given patient Weakening of the arterial wall by inflammation leads to o Aneurysms o Impaired perfusion Æ ischemia Kawasaki Disease x Disease of early childhood (<4y) affecting large-medium and small arteries o Will see kids with MIs o Affects coronary arteries Æ aneurysm/rupture Æ thrombosis Æ acute MIs x Leading cause of acquires heart disease in children x Pathophysiology o Formation of autoantibodies to endothelial & smooth muscle cells ƒ B cell activation and cytokine release o T cells mediate delayed-type hypersensitivity reaction o Infectious agents are more likely the trigger (cross-reactivity) x Clinical Findings o Conjunctival and oral erythema/ulcer x o Edema of hands and feet ƒ Erythema in palms and soles o Desquamative Rash (shedding of skin) o Cervical lymphadenopathy o Up to 20% of untreated patients develop cardiovascular disease ƒ Aneurysm & rupture ƒ Thrombosis ƒ MI – Sudden death Treatment o IV Ig therapy o Aspirin ƒ Normally contraindicated in children   .

mucous membranes. kidney & muscle x Necrotizing glomerulonephritis x Pulmonary capillaritis x Pathogenesis o Associated with P-ANCA (MPO-ANCA) o IC deposition ƒ Antibody response to drug (penicillin) bacteria (strep) or tumor protein antigens o Recruitment and activation of neutrophils ƒ Leukocytoclastic vasculitis à Destructive infiltration and degranulation of neutrophils o Segmental fibrinoid necrosis of tunica media ƒ Without granulomatous inflammation . lungs. heart.  Microscopic Polyangitis x Necrotizing vasculitis of capillaries. and venules x Broad systemic involvement of: o Skin. GI tract. brain. arterioles.

   x Treatment o Cyclophosphamide & steroids  o Renal and brain involvement are difficult to treat Wegner Granulomatosis x Necrotizing granulomatous vasculitis of small/medium sized arteries x Affects males > females. usually in 40y x Clinically resembles PAN o Distinction is in the respiratory system o Respiratory system involved in Wegner ƒ Not involved in PAN x Pathophysiology o T cell mediated hypersensitivity reaction (to inhaled agents) o PR3-ANCAs (C-ANCAs) present o Responds to immunosuppressive therapy o 80% of untreated patients die within 1 year .

neuritis.  x x Clinical Features o Chronic sinusitis o Nasopharyngeal ulceration o Persistent pneumonitis o Renal disease. failure o Rashes. fever Morphologic Features o Necrotizing granulomas ƒ Central necrosis ƒ Fibroblastic proliferation ƒ Giant cell reaction ƒ Mononuclear infiltrate ƒ Glomeruli of kidney affected . hematuria. articular involvement. muscle pains.

  Thromboangiitis Obliterans (Buerger Disease) x Vasculitis of medium and small arteries o Especially tibial & radial arteries x Most commonly seen in young cigarette smokers (<35y) x Pathogenesis o Direct endothelial cell toxicity to tobacco component ƒ Patients are hypersensitive to tobacco extracts o Impaired endothelial-dependent vasodilation when given Ach o Clinical Features ƒ Raynaud ƒ Claudication induced by exercise ƒ Severe pain at rest à Due to neural involvement ƒ Unhealing ulcers of toes. feet. fingers .

à x x Gangrene Vascular insufficiency Æ gangrene Smoking cessation reduces progression Vasculitis Assocaited with other Disease x RA x SLE x Mixed cryoglobulinemia x Antiphospholipid Antibody Syndrome x Henoch-Schönlein purpura Infectious Vasculitis x Vessel wall inflammation due to colonization by infectious pathogens o Subsequent immune complex deposition and Ab crossreactivity x Can lead to weakening of vessel wall and mycotic aneurysms x Examples o Bacterial pneumonia – pulmonary hemorrhage o Bacterial meningitis – brain infarction o Aspergillus & Mucor .

and tongue o Pathophysiology unknown ƒ Structural vessel wall abnormalities ƒ Deficiencies in autonomic control o More prevalent in women in 20-30s . ears.ƒ Vasoinfective fungi Vascular Hyper-reactivity x Not vasculitis. but I put it here… x Raynaud Phenomenon o Recurrent vasospasms of the fingers and toes in response to stress or cold o Primary Raynaud (Raynaud Disease) ƒ Vasospasm with no association of systemic illness o Secondary Raynaud ƒ Vasospasm associated with autoimmune disease à Scleroderma à Mixed CT disease o 3 Phases of color change ƒ Initial white (vasoconstriction) ƒ Blue (cyanosis) ƒ Red (rapid blood reflow)  o Changes are reversible ƒ Must be distinguished from the irreversible causes of ischemia such as vasculitis & thrombosis o Most commonly affects fingers and toes ƒ Can also affect nose.

locally destructive à Do not regress on their own à Von-Hippel-Lindau disease they are present in the retina.Hemangioma x Tumors of blood-filled vessels x Often present at birth x Most commonly seen in head and neck o Can also be present in internal organs such as liver x Classification based on histological appearance o Capillary Hemangiomas ƒ Strawberry Hemangiomas à Found in newborns à Disappear on their own  ƒ ƒ Pyogenic Granulomas   Cavernous Hemangiomas à Composed of larger vascular channels à Circumscribed. CNS. and liver . pancreas.

  .

or axilla of newborns o Unencapsulated growth pattern ƒ Makes them difficult to excise ƒ Penetrate into muscles and other structures  .  Lymphangiomas x Equivalent to hemangiomas in the lymphatic system x Capillay (simple) x Cavernous (Cystic Hygromas) o Can present as huge tumors in the head. neck.

Bacillary Angiomatosis x Vascular proliferation secondary to Bartonella infection o Affects immunocompromised patients x Bartonella henselae o Cat-scratch disease x Bartonella Quintana o Trench fever transmitted by body lice o Silver staining below highlights bacilli in bacillary angiomatsis in an AIDS patient   Kaposi Sarcoma x Caused by HHV-8 x Most commonly affects AIDS patients o An AIDS-defining illness x Elderly and immunosuppressed also affected x Viral infection leads to uncontrolled cellular proliferation by disruption of Cyclin D & P53 x Cutaneous lesions progress from patches Æ plaques Æ nodules .

infiltrating.Angiosarcoma x Malignant vascular neoplasm x Composed of rapidly proliferating. anaplastic cells x Rare malignancy o No association to special settings x Hepatic Angiosarcomas are associated with exposure to o Vinyl chloride monomer (VCM) o Polyvinyl chloride (PVC) o Arsenic containing insectisides and Thorotrast x Angiosarcoma can occur during treatment for primary breast carcinoma o Cutaneous angiosarcoma after breast lumpectomy. axillary lymph node dissection and radiotherapy .