Heart - Dr. Nowacki Atherosclerosis/vasculitides/aneurysms Lecture Ii

Front 1

Back 1

Evolution of arterial wall changes in the response to injury hypothesis. 1, Normal. 2, Endothelial injury with adhesion of monocytes and platelets (the latter to sites where endothelium has been lost). 3, Migration of monocytes and smooth muscle cells into the intima. 4, Smooth muscle cell proliferation in the intima with ECM production. 5, Well-developed plaque

Front 2

describe this pathology

Back 2

hyaline arteriolosclerosis: pink homogenous hyaline thickening of arteriolar walls

what conditions is this seen in?

Hint 2

older individuals
generalized HTN
diabetes
major component of benign nephrosclerosis

Front 3

describ the pathology

Back 3

hyperplastic arteriolosclerosis: onion skin concentric laminated thickening of vessel walls

what is this seen in?

Hint 3

acute elevations or severe HTN -->"malignant HTN"

vasculitides

hypoxemia of pregnancy

Front 4

list the 5 consequences of entothelial injury

Back 4

- Increase permeabillity of vessel wall
- Promote PLT adherence
-Promote monocyte/macrophage
adherence/entry
-Alter vasomotor tone
- Stimulate SMC

Front 5

describe how monocytes are involved in the formation of atherosclerosis, list 5 steps

Back 5

-adhere to altered endothelium
-enter intima
-engulf LDL cholesterol (scavenger pathway)
-oxidize LDL
-Secrete products (IL-1) to recruit more inflammatory cells

Front 6

Once lipoproteins (LDL/VLDL) and lipids have gained entry into vessel wall and are modified by oxidation, what are the three things that OX-LDL does?

Back 6

1. it is cytotoxic to endothelial cells and smooth muscle cells
2. cehmotactic for monocytes, increases monocytes adhesion, inhibits macrophage mobility

Front 7

How to SMCs contribute to atheroslerosis

Back 7

1. they become foam cells = become phagocytic
2. they take up lipids
3. they profliferate in the intima
4. make growth factors : PDGF
5. they make collagen, elastin, glycoproteins

Front 8

what are the consequeneces of atherosclerosis

Back 8

1. narrowed vessels lumen: limited blood flow (no symptoms), reversible ischemia wihth increased demand (claudation walking 10 blocks, angina after exercize)

thrombosis: vessel occluded, sudden severe ischemia, infarct

generate emboli: thrombosis at distant site

weakened wall --> aneurysm

Front 9

what is the definition of an aneurysm

Back 9

abnormal localized dilation of blood vessel

Front 10

differentiate between a true aneurysm and a false aneurysm

Back 10

a true aneurysm is bound by all 3 arterial walls components, where as a false aneurysm is a breach in the vessle wall leading to a hematoma that communicates with the intravascular space

Front 11

what are the two most important causes of aneurysms?

Back 11

atherosclerosis and cystic medial degeneration

Front 12

what are some other causes (notes list 4)

Back 12

infection (mycotic aneurysm), vasculitis, trauma, congenital defects

Front 13

List 3 true aneurysms and 1 that can be both

Back 13

Atherosclerosis
syphilis
congential (berry)

MI if the ventricular wall is intact

Front 14

List a false aneurysm and 1 that can be both

Back 14

vascular graft leak,

also MI if the ventricular wall ruptures

Front 15

what is cystic medial degeneration

Back 15

- elastic fragmentation and clefts filled with ECM (not truly cysts)

**Inflammation and necrosis are ABSENT

-accompanies Marphan Syndrome

Front 16

what infection leads to a mycotic aneurysm

Back 16

salmonella gastroenteritis

Front 17

notice the true aneurysm on the left with all 3 layers buldgin out. On the right, in the false aneurysm, only the adventitia is buldging out, the break is in the media and intima

Back 17

If breaks back in to the lumen = double barrel

If breaks out of adventitia = rupture

Front 18

Why wouldn't you have an abdominal aortic aneurysm fixed as soon as you knew about it?

Back 18

High operative mortality --> 5% for unruptured and >50% if ruptured

Front 19

What is the most common location for aneurysm?

Why?

Back 19

Between the renal arteries and aortic bifurcation -->according to Goljan it is because there is no vaso vasorum below the renal artery, and makes it more susceptible to ischemic damage and atherosclerotic build up

Front 20

What is a common co-existing problem? why?

Back 20

ischemic heart dz -->because both processes are secondary to atherosclerosis

Front 21

% risk of rupture of a given aneurysms in the size: <4, 4-4.9. 5 - 5.9, >6

Back 21

Robbins:
<4=0%
4-4.9 = 1%
5-5.9 = 11%
>6 = 25%

Notes:
<5 - minimal risk
>5 - 5-10% risk
>6 - 25% risk

Front 22

what demographic does abdominal aortic aneurysm typically occur in?

Back 22

men > 50

Front 23

what causes thoracicc AA?

Back 23

syphillis (causes obliterative endarteritis of vasa vasorum that results in ischemia of media and loss of elastic tissue

giant cell arteritis

Front 24

how is syphillitic "tree-barking" caused?

Back 24

contraction of fibrous scars that wrinkles the intervening uninvolved intima

Front 25

what are 2 other syphillitic aortitis complications

Back 25

1. atheromatous involvment of aortic root (may occlude coronary ostia)

2. aortic ring dilation leading to aortic valve insufficiency and massive LV hypertrophy called cor bovinum or cows heart

Front 26

what condidtions is aortic dissction seen

Back 26

marfans syndrome
HTN
iatrogenic
pregnancy

(Rarely see in atherosclerosis or syphillis)

Front 27

what is the most common cause of dissection

Back 27

cystic medial degeneration

Front 28

what isthe genetic defect cause of Marfans

Back 28

AD defect in fibrillin

Front 29

what are the two types of aneurysms

Back 29

A - ascending aorta or entire aorta

B- below subclavian

Front 30

what are the symptoms of syphillitic aneurysm

Back 30

heart failure, impigement of surrounding thoracic organs, rarely rupture

Front 31

what is the pathogenesis of syphillitic aneurysms

Back 31

-Arise in tertiary syphillis

- inflammation of vasa vasorum with eventual obliterative endarteritis,

**plasma cells common

Front 32

name the pathology here and the underlying dz

Back 32

"tree barking" due to syphillis -->which leads to ischemic injury and and scarring of the aorta

Front 33

define aortic dissection

Back 33

dissection of blood along laminar planes of aortic media forming a blood filled intramural channel -

- rupture = massive hemorrhages +/- sudden death

Front 34

What are the 2 groups that aortic dissection typically occurs in?

Back 34

1. Men 40-60 who are hypertensive - nonspecific degenerative histologic changes

2. People with connective tissue diseases affecting the aorta (Marfan)

Front 35

Describe Marfan's syndrome

Back 35

marked elastic tissue fragmentation and disruption with cystic/clefted spaces containing amorphous extracellular matrix = CYSTIC MEDIAL DEGENERATION -->defect in fibrillin gene

Front 36

describe the pathology on the which side? compare to the normal

Back 36

the pathology shown is of marfans with cystic medial degeneration, a marked elastin fragmentation, that form areas devoid of elastin that resembles cystic spaces

the right is normal - showing layered pattern of elastic matrix

Front 37

what is the clinical presentation of aortic dissection

Back 37

sudden onset of excruciating pain starting int he anterior chest and radiating to the back -->often described as "RIpping" or "Tearing"

- pain moves down as dissection descends

Front 38

KNOW KNOW KNOW

what is the most common form of vasculitis seen in adults?

Back 38

Temporal arteritis

Front 39

what is the most common form of vasculitis seen in children

Back 39

Henoch- Schenlein purpura

Front 40

Define Vasculitis

Back 40

Inflammation of the vessel wall / vessel destruction

-can affect large and small vessles
-wide spectrum of clincial manifestations
-can be a direct infection/immunologic/unknown

Front 41

in the pauci-immune vasculitides, what is the target antigen for Cytoplasmic or cANCA

Back 41

PR3 - (protinase) a neutrophilic granule

Front 42

in the pauci-immune vasculitides, what is the target antigen for Perinuclear or pANCA

Back 42

MPO (myeloperoxidase)

Front 43

what is typically found in (ancas) in wegener's granulomatosis?

Back 43

cANCA (95%)

Front 44

what is commonly found in microscopic polyangitis?

Back 44

pANCA

Front 45

what is typically found in Churg Strauss

Back 45

pANCA

Front 46

How are ANCAs used clinically

Back 46

quantitative diagnostic markers - the levels reflect the degree of inflammatory activity and recurrence

can be used to monitor therapy as well

Front 47

what vasculitides affect large vessels, including the aorta, large branches to the extremeties, head and neck

Back 47

giant cell (temporal) arteritis

takayatsu arteritis

Front 48

what vasculitides affect medium vessels, including the main visceral arteries and their branches

Back 48

polyarteritis nodosa

kawaski disease

Front 49

which vasculitides affect small vessels, including arterioles, venules, capillaries, and occasionally small arteries

Back 49

Wegener granulomatosis

Churg-Strauss Syndrome

Microscopic polyangitis

Front 50

Back 50

Hint 50

Figure 11-23 Giant-cell (temporal) arteritis. A, H&E stain of section of temporal artery showing giant cells at the degenerated internal elastic lamina in active arteritis (arrow). B, Elastic tissue stain demonstrating focal destruction of internal elastic lamina (arrow) and intimal thickening (IT) characteristic of long-standing or healed arteritis. C, Examination of the temporal artery of a patient with giant-cell arteritis shows a thickened, nodular, and tender segment of a vessel on the surface of head (arrow). (C from Salvarani C et al.: Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med 347:261, 2002.)

Front 51

which large vessel vasculitide is associated with polymyalgia rheumatica?

Back 51

giant cell temporal arteritis

Front 52

which large vessel vasculitide occuris in patients under 50?

Back 52

Takayasu

Front 53

Which medium vessel vasculitide is associated with mucocutaneous lymph node syndrome?

Back 53

kawaski

Front 54

what is mucocutaneous lymph node syndrome

Back 54

acute self limited syndrom with fever, conjunctival and oral erythema, desquamating skin rash, cervical lymph node enlargement

Front 55

which small vessel vasculitide contains eosinophil-rich granulomas of respiratory tract

Back 55

Churg strauss syndrome

Front 56

what 2 other features may be found in churg strauss?

Back 56

asthma and circulating eosinophilia

Front 57

Necrotizing glomerulonephritis is common in which two small vessel vasculitides?

Back 57

Wegener and microscopic polyarteritis

Front 58

which is the "pulseless disease"

Back 58

Takayasu (weakening of the upper extremity pulses due to intimal thickening)

Front 59

which large vessel vasculitide affects the aortic arch?

Back 59

takayasu

Front 60

which vessel vasculitis is assocated with Hepatitis B in 30% of cases?

Back 60

Polyarteritis Nodosa

Front 61

What is the leading cause of heart disease in kids/

Back 61

kawasaki (20% develop cardiac sequelae)

Front 62

how is kawasaki treated

Back 62

aspirin and IV gamma globulin

Front 63

which has lesions of the same age that affect vessels?

Back 63

microscopic polyangiitis/leukocytoclastic vasculitis

-in contrast to polyarteritis nodosa, where different stages of lesions may be present in the same vessels or other vessels

Front 64

what HLA is associated with Beurger's disease?

Back 64

Buerger(thomboangiitis obliterans) is associated with HLA-A9 and HLA-B5

Front 65

What is rare about the histologic inflammatory process associated with Buerger dz

Back 65

the thrombus may contain microabcesses and the inflammation may extend through the vessel wall to involve veins and nerves

Front 66

what infectious agent invades vessels

Back 66

fungus in diabetics - aspergillus and mucor

Front 67

how are lymphangiomas distinguished from hemangiomas?

Back 67

by the absnse of blood in the spaes (may also see lymphatic valves)

Front 68

what is the painful tumor of the digits called

Back 68

glomus tumor - excision is curative

Front 69

with what infectious agent is bacillary antiomatosis associated?

Back 69

Bartonella henselae (causes cat scratch fever in immunocompetent people, cat flea vector)

b quintonna (causes trench fever in WWI soldiers, louse vector)

Affects immunocompromised HIV pts

Front 70

with what infectious agent is Kaposi's sarcoma associated

Back 70

HHV-8

Front 71

General Vasculitis facts:
-requires evidence of what?
-type of inflamation?
-classification based on?

Back 71

Must have evidence of vessle wall damage (ie thrombi, granuloma)

- inflammation can be granulomatous

-classification based on **size of vessel (hist & loc), pathogenesis, and clinical presentation

Front 72

what types of infection lead to vasculitis

Back 72

viral, fungal, bacterial, ricketsial, spirochetal

Front 73

What non-infectious causes of vasculitis

Back 73

-**most important is Immunologic injury -->more likely to have systemic complications

immune complex (HSP, SLE), Direct Ab Attack (goodpastures), ANCA assoc, cell mediated (transplant)

Front 74

what type of vasculitis is ANCA (antineutrophil cytoplasmic antibodies) helpful with? what does it correlate with? how is it demonstrated

Back 74

it is demonstrated by immunoflorescent assays

- very helpful in patients with small vessel vasculitis

- correlates with active disease and disease severity

Front 75

what type of inflammation is seen in both large vessel vasculitides

Back 75

granulomatous

Front 76

what are the main differences between temporal and takayasu's

Back 76

temporal is in older people affecting the temp artery, with flu like prodrome and point tenderness, and blindness, increases Sed Rate

where takayasu is in youger patients, it affects the aortic arch and major branches, is called "pulseless disease" (UE only, LE fine), can have visual defects,

Front 77

describe pathology

Back 77

takayasu - in upper left see giant cells, mediated by lymphocytes, has a prediliction for women, and japanese

Front 78

describe the pathology

Back 78

PAN - this is segmental necrosis, (note the fibrin in the bottom left of the lumen, but relatively normal lumen at the top right. ) with thrombotic occlusion of lumen of sm artery

Front 79

describe the pathology

Back 79

PAN - small aneursyms at vessel bifurcation are common

-endothelium is gone or replaced by thrombus,

-in the midddle pciture note hte dense inflamatory cells, with no muscles cells

-systemic symptoms

Front 80

with PAN what demographic is typically involved?

Back 80

all ages, often younge adults -->presents with fever malaise and weight loss

Front 81

List the organs PAN typically does and does NOT affect

Back 81

PAN can affect the GI, muslces, other systems,

NOT THE LUNG
can affect KINDEYS --.NO GLOMERULONEPHRITIS

Front 82

List the important features of PAN

Back 82

can involve smaller vessels, but not arterioles

SEGEMENTAL disease involves sharply demarcated portions of affected vessels that often have secondary thrombosis leading to distal ischemic injruy

Front 83

PAN important association

Back 83

HEPATITS B

Front 84

what is an acute illness in children and infants, presents with fever, lyphadenopathy, skin rash, oral/conjunctivital erythema, and affects CORONARY ATERITIS (20%)

Back 84

Kawasaki - legions histo sim to PAN

tx with Immunoglobulins NOT steroids

coronary arteritis important becuase it kills people

Front 85

List the immune complex smal vessel vasculitides

Back 85

Henoch-Schlonlein purpura
immune complex GN
cryoglobulinemia
graft rejection
SLE/RA

Front 86

Describe the presentation of Microscopic Polyangiitis (polyarteritis, leukocytoclastic vasculitis)

Back 86

-ALL lesions at same stage
-INVOLVES KIDNEYS & LUNGS
-palpabel purpuras
-**P-ANCA
- neutrophils in whole and frag forms inflitrating vessel walls and causing fibrinoid damage

Front 87

Churg-Strauss

Back 87

necrotizing vasculitis + granulomas

EOSINOPHILS -->strong association with allerigic rhinitis and bronchial asthma, often persipheral eosinophilia

p-ANCA in Half

Front 88

What is wegener's triad

typically found in 40 yo men, c-ANCA in majority

Back 88

necrotizing granulomatous vasculitis,

necrotizing granulomas of URT, LRT, & both

renal dz -->with glomerulonephritis

Front 89

Henoch-Schonlein purpura characterized by purpuric skin lesions, what does it present with and what are other clinical findings?

Back 89

Presents with abdominal pain

IgA dominant immune complex deposits in capillaries, venules, and arterioles

See palpable purpuras on buttocks and lower extremities, hematuria, polyarthritis

Front 90

what type of vessel does buerger dz affect and what type inflammation is it?

Back 90

it affects the small/medium arteries and veins.

it is segemental thrombosing acute and chronic inflammation, that is VERY PAINFUL

Front 91

who does buergers dz primarily affect

Back 91

younge male smokers

Front 92

Buergers may lead to gangrene, what are the tx

Back 92

quit smoking, may slow progression. Otherwise can progress to amputation

Front 93

what is the difference between raynaud disease and phenomenon

Back 93

Disease is paroxsymal pallor/cyanosis of finger tips and toes, that is secondary to vasospasm of the small arteries and arterioles. It is common in younge women as a exaggerated vasomotor response to cold/stress

Whereas, phenomenon is extremity arterial insufficiency secondary to arterial narrowing dute to other conditions/dz

GIVE red-white-blue

Front 94

what are the two venous diseases

Back 94

varicose veins and thrombophlebitis

Front 95

what is the common clinical finding of varicose veins

Back 95

ulcers and stasis dermatitis often develop

Front 96

what causes varicose veins

Back 96

they are abnormally dilated tortous veins esp in LE, secondary to chronically elevated pressures, valves become incompetent.

-luminal thromosis can occur but emboli are rare

Front 97

What is thrombophlebitis

Back 97

venous inflammation

Front 98

what does DVT lead to

Back 98

Pulmonary Emboli

Front 99

What is Trousseau Syndrome

Back 99

multiple venous thrombi in the setting of malignacy (espcially adenocarcinoma)

Front 100

What are the four types of hemangiomas

Back 100

Capillary
Juvenile capillary (strawberry)
cavernous
Pyogenic granuloma (lobular capillary hemaniogman

Front 101

What is the cause of 7% of all bening tumors in children

Back 101

hemangiomas

Front 102

Which type of hemangioma can be seen in Von Hipple Lindau? what other organ is common?

Back 102

Cavernous -- common in the liver

-large cavernous vascular channels

Front 103

which is the most common hemangioma, how is it characterized

Back 103

the most common is capillary and it is skin and mucous membranes, close packed aggregates of capillary sized vessels

Front 104

Describe Juvenile capillary hemangioma

Back 104

present at birth, rapid growth then involution (most gone by 7)

Front 105

when is pyogenic granulomas most often seen

Back 105

they are often seen after trauma or pregnancy --> often ulcerated, polypoid variant of capillary hemangioma

Front 106

what are the 4 forms of Kaposi's

Back 106

1. chronic/classic/european = older men eastern europe, red purple plaques of LE, relapses and remissions, skin ONLY

2. AIDS related = homosexual males, lesions anywehere in skin/oral & visceral mucosa

3. Lymphadenopathic/African - younge men in equatorial aftrica, restricted to LN, aggressive

4. Transplant associated = cutaneous and visceral involvement, lesions may regress with discontinuation of immmunosuppresion -->MOST AGGRESSIVE Type

Front 107

What are the 3 histological stages of all types of Kaposi's

Back 107

Patch -->Plaque--> Nodular

histology - spindle shaped blood vessels, plasma cells admixed.

infected with HHV-8

Front 108

Leukocytoclastic Vasculitis

(not really in the notes but in the learning objectives)

Back 108

definition; Acute vasculopathic hypersensitivity disorder characterized by leukocytoclasis and fibrinoid necrosis of small venules in the dermis.

presentation: palpable purpura or erythematous macules, usually on dependent parts, especially the lower legs
Pathogenesis: Involves deposition of immune complexes in vessel walls with activation of complement:70
◦results in:
■chemotaxis of neutrophils
■injury to vessel walls with exudation of:
■serum
■erythrocytes
■fibrin

Front 109

scavenger pathway

(LO not really in notes)

Back 109

Robbins talks about a scavenger receptor on macrophages (not the regular LDL rec) that helps the macrophage eat oxidized LDL transforming them into foam cells.