Y2S1B2 - Path - Vascular Diseases

Front 1

What pattern of arteriosclerosis is seen in patients older than 50 and is caused by calcified deposits in muscular arteries, that do not narrow the arterial lumen?

Back 1

Monckeberg medial sclerosis

Front 2

Arteriolosclerosis affects small arteries and arterioles and is a/w what 2 conditions? What are the 2 different types of arteriolosclerosis?

Back 2

HTN & diabetes

hyaline and hyperplastic

Front 3

Atherosclerosis principally affects which types of arteries?

Back 3

Elastic and medium-sized arteries

Front 4

What lesion is commonly found in children, as early as <1 yr of age, and is composed of foam cells in the intima?

Back 4

Fatty streak

Front 5

What are the MC vessels involved in atheromatous plaques?

Back 5

Abdominal aorta, coronary arteries, popliteal arteries, internal carotid arteries and Circle of Willis

Front 6

What are the components of an atheromatous plaque?

Back 6

They are raised nodular lesions within the intima.

Fibrous cap - extracellular matrix, scattered cells
Necrotic (lipid) core - cell debris, cholesterol crystals, foam cells

Front 7

What causes "pipestem" arteries or an "eggshell" aorta?

Back 7

Calcification of atheromatous plaques

Front 8

What causes a superimposed thrombus or atheroemboli?

Back 8

Ulceration (erosion, rupture) of atheromatous plaques

Front 9

What complication of an atheromatous plaque can cause an aneurysm?

Back 9

Involvement of the media, leading to weakness of the vessel wall

Front 10

Familial hypercholesterolemia (the MC inherited disorder of lipoprotein metabolism) is caused by a mutation in what gene?

Back 10

LDL receptor gene

The LDL receptor is required for uptake of LDL. Affected pts have increased LDL in plasma, leading to accelerated atherosclerosis.
heterozygotes - 2-3 fold inc in cholesterol
homozygotes - 5-6 fold inc in cholesterol

Gene therapy can be used.

Front 11

Describe the mutation (monoclonal theory) as a possible cause for VSMC proliferation in atheromas.

Back 11

Oncogenic viruses linked to atherosclerosis
plaques induced w/ mutagenic chemicals
genetic damage IDed in plaque cells
Cig smoke is a potent atherogen

Front 12

Describe the epigenetic alterations theory as a possible cause for VSMC proliferation in atheromas.

Back 12

Plaque cells shown to exhibit overexpression of proto-oncogenes
benzopyrene induces overexpression of c-Ha-ras and c-myc protooncogenes

Front 13

___% of individuals have HTN, and ___% of hypertensives develop malignant HTN (diastolic >120).

Back 13

25%, 5%

Prevalence is a function of age, race, and diet

Front 14

What are some inherited and acquired causes of an increase in renin?

Back 14

Inherited:
Fibromuscular dysplasia

Acquired:
Renal artery stenosis
Renin-secreting tumor

Front 15

What are some inherited and acquired causes of an increase in angiotensinogen?

Back 15

Inherited:
Angiotensinogen variants

Acquired:
Oral contraceptives

Front 16

What are some inherited and acquired causes of an increase in mineralocorticoids?

Back 16

Inherited:
Glucocorticoid-remediable aldosteronism (aldosterone synthase)
11beta-Hydroxylase defic
17alpha-Hydroxylase defic

Acquired:
Aldosteronoma

Front 17

What are some inherited and acquired causes of an increase in mineralocorticoid receptor activity?

Back 17

Inherited:
AME (11beta-HSD)
Glucocorticoid resistance

Acquired:
Licorice Ingestion
Cushing syndrome?

Front 18

What are some inherited causes of increased Na reabsorption via the NaCl transporter OR epithelial Na channel?

Back 18

NaCl transporter:
Gitelman syndrome

Epithelial Na channel:
Liddle syndrome (beta or gamma subunit)
Pseudohypoaldosteronism-1 (alpha or beta subunit)

Front 19

Deficiencies of what enzymes result in shunting of steroidogenesis into the mineralocorticoid pathway, resulting in increased production of mineralocorticoids?

Back 19

11beta-Hydroxylase and 17alpha-Hydroxylase

Front 20

What is the name of an inherited disorder resulting in overexpression of the aldosterone synthase gene, which in turn results in excessive production of aldosterone?

Back 20

GRA (Glucocorticoid-remediable aldosteronism)

Front 21

An enzyme is expressed in the renal tubular cells and converts cortisol (which has some mineralocorticoid activity) to cortisone (which does not have any mineralocorticoid activity). A deficiency of this enzyme allows cortisol to accumulate in the renal tubular cells, resulting in increased stimulation of the mineralocorticoid receptor and excessive reabsorption of sodium.

What enzyme is this? What inherited disorder is its deficiency?

Back 21

11beta-hydroxy steroid dehydrogenase (11beta-HSD)

AME (Syndrome of apparent mineralocorticoid excess). This is an inherited disorder in which the affected individuals have a deficiency of the enzyme.

Front 22

What is the name of an autosomal dominant disorder in which the affected individuals have a gain of function mutation in the gene that encodes for the epithelial Na+ channel in the renal tubular cells? The gain of function mutation in this gene results in excessive reabsorption of Na+ from the renal tubules.

Back 22

Liddle Syndrome

Front 23

What are some environmental factors a/w increased BP?

Back 23

Stress
Obesity
Physical inactivity
Heavy salt consumption* (he had this one in a different color!)


Chinese living in China have a lower incidence of hypertension than Chinese living in USA

Front 24

Describe a vulnerable plaque.

Back 24

Thin fibrous cap
Large lipid core
Tend to have more inflammation, d/t MMPs (matrix metalloproteinases) produced by macrophages, which can degrade collagen in the fibrous cap

Front 25

What are some extrinsic factors that can contribute to plaque rupture?

Back 25

Stress resulting in increased release of catecholamines and spikes in blood pressure

Front 26

Elevated serum levels of what things (name a few) are a/w an increased risk of atherosclerosis?

Back 26

LDL, C-reactive protein, homocysteine

Front 27

Humans do not possess the “enzymatic machinery” to break down (cis/trans) fats. Therefore consumption of (cis/trans) fats increases the incidence of obesity, type II diabetes and atherosclerosis.

Back 27

Trans!!

Front 28

Untreated, malignant hypertension has a ___% mortality rate within 3 months, and a ___% mortality rate within a year.

Back 28

50%, 90%

Front 29

Serum from some patients with vasculitis contains
Ab’s directed against neutrophil cytoplasmic Ag’s (ANCAs).

Which type of ANCA can be induced by various drugs? Which type of ANCA is probably induced by various infections?

Back 29

Drugs - MPO-ANCA aka p-ANCA

Infections - PR3-ANCA aka c-ANCA

Both ANCAs are constituents of neutrophilic granules. ANCA titers correlate very well w/ dz activity.

Front 30

Proposed Pathogenesis of ANCA mediated vasculitis!

a) ____&____ are expressed on the surface of activated neutrophils
b) Drugs, infections, etc., result in formation of Ab’s that ________ with (a) (i.e. ANCAs)
c) Subsequent infection, drug exposure, etc., results in formation of _____________.
d) ANCAs then bind to (a) on the surface of activated neutrophils -> _________ -> _____________

Back 30

a) MPO & PR3
b) cross-react
c) high titer ANCAs
d) degranulation; endothelial injury

Front 31

The following types of vasculitis are ______ mediated.

Infection induced
Henoch-Schönlein purpura
SLE & rheumatoid arthritis
Drug induced
Cryoglobulinemia
Serum sickness

Back 31

Immune-complex mediated

Front 32

The following types of vasculitis are ______ mediated.

Wegener granulomatosis
Microscopic polyangiitis
Churg-Strauss syndrome

Back 32

ANCA mediated

Front 33

The following types of vasculitis are ______ mediated.

Goodpasture syndrome
Kawasaki disease

Back 33

Direct antibody attack mediated

Front 34

What does biopsy of temporal artery in giant cell arteritis show?

Back 34

Mononuclear infiltrate
Giant cells
Focal destruction of internal elastic lamina

Pathogenesis is most likely a cell-mediated immune response against an Ag in the internal elastic lamina.

MC in >50 yo, may cause blindness in one or both eyes

Front 35

Biopsy in Takayasu arteritis would show what?

Other notes about the disease?

Back 35

Mononuclear infiltrates
Giant Cells
Fibrosis

Also:
women <40
pulm arteries 1/2 the time
dec BP and pulse in UE
inc BP in LE
may cause visual disturbances, blindness, dizziness, focal weakness, hemiparesis, pulm HTN

Front 36

If you see a vasculitis with fibrinoid necrosis with involvement of renal arteries and NOT pulmonary arteries, what should you think?


30% of these patients have what complexes?

Back 36

Polyarteritis Nodosa! (segmental transmural inflammation w/ fibrinoid necrosis, thrombosis, aneurysms, fibrosis -> firm nodules)

HBsAg-HBsAb complexes

ALSO:
systemic, necrotizing
small and medium arteries (especially renal, but **PULM arteries are SPARED)
Young adults
episodic
*HTN, fever, malaise, CRF, abd pain, bloody stool, myalgias, peripheral neuritis, skin lesions

Front 37

Fever, erythema & erosions of the conjunctiva & oral mucosa, cervical lymphadenopathy, skin rash, edema of the hands & feet, and erythema of the palms & soles are seen in children with what syndrome?

Back 37

Mucocutaneous Lymph Node Syndrome

The syndrome is usually self-limited.

Kawasaki-affected children manifest these same symptoms!

Front 38

The pathogenesis of giant-cell (temporal) arteritis most likely involves:

a) cell-mediated immune response

b) Deposition of immune complexes

c) ANCA

d) Infection of the arterial wall

e) Endothelial cell autoantibodies

Back 38

A

Front 39

A hypersensitivity rxn, w/ MPO-ANCA (p-ANCA), necrotizing glomerulonephritis, with morphology that may be similar to polyarteritis nodosa (often only infiltration by neutrophils), "pauci-immune" injury is likely what disorder?

Back 39

Microscopic polyangiitis (leukocytoclastic vasculitis)

leukocytoclasia = fragmented nuclei (karyorrhexis) in leukocytes

Front 40

Which vasculitis is a/w asthma, allergic rhinitis, and eosinophilia?

Back 40

Churg-Strauss syndrome


Rare systemic medium to small vessel vasculitis
Fibrinoid necrosis, eosinophilic infiltrates & granulomas
ANCAs (mostly MPO-ANCA) in some cases
Heart, skin, GI tract and kidneys are commonly involved
Cardiac involvement accounts for almost half of all deaths
Appears to be a HS reaction to some Ag

Front 41

What is the triad of Wegener Granulomatosis?

Back 41

1. necrotizing granulomas in the resp. tract
2. focal necrotizing or granulomatous vasculitis affecting small arteries & microvasculature
3. necrotizing or crescentic GN

Front 42

A patient presents w/ bilateral nodular & cavitary lung infiltrates, sinusitis, ulcers in nasopharynx, renal disease, skin rashes, and myalgias.
Cavitary lesions in lungs resemble TB or fungal infection.
a) What vasculitis should you suspect?
b) What is the most likely pathogenesis?
c) ANCA do most patients have?

Back 42

a) Wegener Granulomatosis

b) most likely a cell-mediated hyper-sensitivity reaction to an inhaled Ag (large vessels)

c) Up to 95% of patients have PR3-ANCA (c-ANCA) (small vessels)

Front 43

Thromboangiitis occurs in heavy smokers <35 and is aka?

Back 43

Buerger Disease

Involves medium & small arteries
Much more common in Israel, Japan & India than US
Inc prevalence of HLA-A9 & B5

Morph: acute & chronic inflammation of vessel walls w/ thrombosis, secondary inflammation of nerves & veins

Front 44

What are some causes of a true aneurysm?

Back 44

atherosclerosis**, cystic medial degeneration, congenital defects, infections (mycotic aneurysms), trauma & vasculitis

Rupture is the main complication

Front 45

Which of the following vasculitides is mediated by PR3-ANCA (c- ANCA)?

a) Microscopic polyangiitis
b) Wegener granulomatosis
c) Thromboangiitis obliterans
d) Polyarteritis nodosa
e) Kawasaki disease

Back 45

B

Front 46

Where is the MC site of an aneurysm?

Back 46

In the abdominal aorta, below the renal arteries but above the bifurcation

they're usually atherosclerotic and often contain a mural thrombus

Front 47

What nutritional deficiencies can be involved in the pathogenesis of an aneurysm?

Back 47

Vitamin C
Copper (needed for lysyl oxidase -> collagen crosslinking)

Front 48

Usually there is an _______ tear in aortic dissection.

Back 48

Intimal

The morphology is cystic medial degeneration (fragmentation of elastic fibers in media of aorta)

Front 49

What are the 2 distinct groups that are prone to develop aortic dissections?

Back 49

40-60yo hypertensive men
younger pts w/ Marfan or other CT dz (about 10%)

Front 50

Proximal dissections involve the ascending aorta, either in isolation (DeBakey __) or as part of a more extensive dissection (DeBakey __). Distal or DeBakey __ dissections arise distal to the takeoff of the great vessels.

Back 50

II, I, III

(2, 1, 3)

Front 51

Abnormally dilated, tortuous veins 20 to prolonged increased intraluminal pressure are called what?

Back 51

Varicose Veins

MC site is the superficial veins of the leg
MC seen in people > 50, obese individuals, women, people who stand a lot
Hereditary predisposition
Morph: variation in thickness, thick areas exhibit SM hypertrophy & fibrosis, valvular deformities
Clinical Manifestations: pain, thrombosis, stasis dermatitis, ulceration

Front 52

Which of the following would be least likely to contribute to the development of an AAA?

a) Atherosclerosis
b) Hypertension
c) Inherited defect in connective tissue
d) Overexpression of MMPs
e) Overexpression of TIMP

Back 52

E (would actually be protective)

Front 53

What is the main complication of thrombophlebitis and phlebothrombosis (accounts for about 30% of in-hospital deaths)?

Some other notes about thrombophlebitis and phlebothrombosis... (predisposing factors, symptoms, diagnosis, prevention)

Back 53

Pulmonary Embolism!!

Deep leg veins account for > 90% of cases
Predisposing factors: heart failure, pregnancy, obesity, hypercoagulability states, malignancy, post-op state & prolonged immobilization
Sx’s: few signs or sx’s early, may have edema, cyanosis, heat, tenderness, redness, pain, Homan sign
Diagnostic procedures: ultrasonography, venous angiography
Prevention: muscle exercises, ambulation ASAP, anticoagulant Rx