From inside to out:

Intima:

• endothelium (with subendothelial space containing minimal tissue and ECM)

• Internal elastic lamina

Muscularis Media

Adventitia:

• External elastic lamina
• Adventitial tissue with smaller blood vessels to support the musular layers

Aorta: the most elastic fibers of any vessel. significant amount of fibrous tissue. Less smooth muscle than fibrous tissue. Meant to withstand a lot of pressue and to provide recoil and continue to generate pressure after the initial outflow of blood from the heart.

Artery: Transition to more smooth muscle than elastic tissue. Fibrous tissue makes up the smalles component. Begin to see where the contraction and relaxation of arteries can impact SVR.

Arterioles: Where the real control of systemic blood pressure occurs. Smooth muscle predominates. There is slightly more fibrous tissue than elastic tissue. Thanks to parallel circulation, the overall pressue in these vessels is decreasing, but control of diameter via smooth muscle is a powerful modulator of BP.

Precapillary sphincter: almost entirely smooth muscle with a touch of elastic and fibrous tissue.

Capillary: entirely endothelium with perhaps a layer of pericytes to control permeability. Large parallel circulation and control from the sphincters allows only a thin cellular tube to distribute nutrients from blood.

Veins: larger diamerters, larger lumens, thinner  and less organized walls (layer wise) than arteries. Easier for tumors and inflammation to penetrate them.

Venule: Pericytes plus some fibrous tissue make up the final resorptive area of the end capillary circulation.

Vein: Almost equal parts elastic, fibrous, and smooth muscle. Allows for storage of blood with relaxation and contraction.

Vena Cava: Very large and floppy. Roughly equal fibrous tissue and smooth muscle. Half as much elastic tissue as either of the other components. Once again, storage and strength to receive and maintain a large fraction of the body's blood

What is an AV fistula?

A arterio-venous fistula is an abnormal connection between arteries and veins.

May be secondary to trauma or healing from a previous dilation or inflammatory process.

They may also be made surgically (example, for hemodialysis)

Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic disorder that leads to arterial stenosis, aneurysm, and dissection. It has been observed in nearly every arterial bed. The most often involved arteries are the renal and internal carotid arteries, and less often the vertebral, iliac, subclavian, and visceral arteries. FMD may rarely occur in the coronary arteries.

(from Up to Date)

characterized by fibrous thickening of the intima, media, or adventitia of the artery. (wikipedia)

A congenital condition, Fibromuscular dysplasia is an autosomal dominant^[4] disorder. It tends to occur between 14 and 50 years of age

An intracranial berry aneurysm, also known as a saccular aneurysm, is a sac-like outpouching in a cerebral blood vessel, which can seem berry-shaped, hence the name. Once a berry aneurysm has formed it is likely to rupture, causing a stroke. Thus they are serious medical emergencies, and should be treated as soon as possible.

Intracranial berry aneurysms are the most common kind of aneurysm in the brain. Their incidence is 1 in 10000 people per year (around 27,000 cases per year in the United States). They have a mortality rate of 70–90%.

Berry aneurysms are usually found in the region of the Circle of Willis. (Wikipedia)

These are congenital in nature, a result of intrinsic vessel wall weakness.

What are some anticoagulant substances secreted by endothelial cells?

(4)

Prostacyclin

Thrombomodulin

Heparin-like molecules

Plasminogen activator (Plasminogen breaks up fibrin clots)

What are some Procoagulant molecules produced by endothelial cells?

(3)

vWF

Tissue Factor

Plasminogen activator inhibitor

You just kind of with the endothelium would make up its mind.

Endothelial cells also modulate blood flow by stimulating contraction and relaxation of the blood vessels. What are some of the effector compounds?

Vasoconstrictors:

Endothelin (recall, this is very potent and causes an initial vasoconstriction during inflammation and injury)

ACE

Vasodilators:

NO

Prostacyclin

If you can recall from block one, what are some mediators of inflammation and immunity released by endothelial cells?

IL1, IL6, chemokines

Adhesion molecules (ICAM, VCAM, PCAM, E & P selectin)

MHC I (II if in chronic inflammation)

Turbulent flow (plaque build up, HTN)

Cytokines

Complement

Bacterial products

Lipid products

Hypoxia/acidosis

viruses

cig. smoke

Aside from vasodilation and vasoconstriction, what good are vascular smooth muscles?

Make ECM proteins

Make growth factors and Chemokines

Can Migrate and proliferate for angiogenesis

What factors Promote smooth muscle growth and proliferation?

What factors inhibit it?

Promote:

PDGF, Endothelin 1, Thrombin, FGF, IFNgamma, IL-1

Basically, inflammation as a means of repair.

Inhibitors:

Heparin sulfates, NO, TGF-Beta

Though smooth muscle proliferation is good for angio and vasculogenesis, it can also be a problem, leading to vasculitis.

Give a brief overview of why this might be...just a couple line.

1. Atherosclerosis
2. Monkeberg's Medial Calcific Sclerosis
3. Arteriosclerosis

Atherosclerosis is the most frequent and important form of arteriosclerosis. What sized blood vessels does it mainly affect?

Medium to Large sized Muscular arteries in addition to Large elastic arteries. It is the intima that is progressively damaged and altered in these vessels.

From Most frequent locations to least...

Abdominal Aorta>Coronary arteries>popliteal arteries>descending thoracic aorta>Internal carotids>Circle of Willis

What is the hallmark formation seen in Atheroscleromas?

A fibrofatty plaqu that protrudes from the intima and blocks the lumen of the blood vessel. It also serves to weaken the vessel walls.

This structure is refered to as an Atheroma ("oma" like its a tumor of the vessel)

Describe the AHA classifications of atherosclerotic lesions.

It makes sense as a progession and can help get a process in your mind. Try to include a timing or clinical correlation with the descriptions.

Type 1: Mainly due to natural process of lipid accumulation in the first couple decades of life. Macrophages appear in the intima to clean up the lipids. No clinical consequences.

Type 2: More lipids accumulate through the third decade of life. There are intracellular inclusions now as cells visibly store the fat. These are termed "fatty Streaks" and often happen around the Ostea of blood vessels coming from the aorta. Still, clinically silent.

Type 3: From about the third decade of life, small bits of lipids will begin to accumulate extracellularly. These accumulations are called "intermediate" lesions. Still, likely to be clinically silent.

Type 4: Type 2 processes continue and a larger Core of lipids is developing. This core signifies the beginning of an Atheroma. There may begin to be clinical symptoms.

Type 5: From the fourth decade of life, the atherotic core or multiple cores develop fibrous caps and increasingly occlude the vessel lumen. There can also be calcification of these cores with associated fibrous coverings. smooth muscle and collagen deposition are occuring. These are termed "fibrous Atheromas".

Type 6: "complicated Lesions" there is a surface defect in the atheroma, probably ulcerations that can increase a persons risk for clotting and the development of Thromboses or Hemorrhages/hematomas of the vessel walls.

What are some complications of Atherosclerosis?

(straight from the notes)

(5)

Myocardial infarction

Cerebral Infarctin (Stroke)

Aortic Aneurysms

Peripheral Vascular Disease

Other: Diminished arterial perfusion (gangrene) -- mesenteric occlusion, pursuant to dead bowel (very bad), Chronic ischemic heart disease

What are the components of a atherosclerotic plaque?

Superficial fibrous cap: Smooth muscle cells, leukocytes (macrophages, lymphocytes), dense connective tissue, ECM

Necrotic lipid core: full of foam cells, cholesterol clefts, dead cells

Periphery: neovascularization

Plaques often undergo calcification.

Hyperlipidemia (diet, pills,exercise)

Hypertension (ditto)

Cigarette smoking

Diabetes (ditto to the ditto)

Ideally, your cholesterol should be less than ____ mg/dL.

___ cholesterol is better to have than ___ cholesterol.

Defects in what family of genes and receptors throw off the balance of good and bad cholesterol?

150 mg/dL

HDL is better than LDL

Apo-lipoproteins/LDL receptor (ex. Familial Hyperlipidemia)/lipoprotein lipase

Also...Statins inhibit HMG-CoA reductase, important in cholest. biosynth.

Type IIa hyperlipoproteinemia:

What is the defect and what would you see reflected in the specific cholesterol levels?

Defect in LDL receptor OR Apolipoprotein E

high LDL

Type IIb hyperlipidemia

What is the defect and how would cholesterol levels reflect this?

Defective LDL receptor OR Apolipoprotein B

High chol. and trigs

esp. LDL and VLDL

Type IV hyperlipidemia

What is the defect and what would the cholesterol levels look like?

Defect is in lipoprotein lipase

High trigs and High VLDL

Familial Hypercholesterolemia

This is a primary disorder of cholesterol metabolism. The defect is ___________.

How does the degree of Atheroscleromas compare for hetero and homozygotes?

LDL receptor defect.

heterozygotes have LDL levels 2-3 X norm. They have premature AS and Xanthomas

Homozygotes have 5-10 X norm LDL levels. Severe AS in childhood

What are some secondary causes of hyperlipidemia?

Dense card, try to break it down and recognize them if you can't think of them off the top of your head.

Diet

Alcohol: elevated triglycerides (recall fatty liver disease)

Endocrine disorders:

DM, Hypothyroidism (down regulated LDL receptors)

Estrogens/Progestins (OCP -- oral contraceptive pill, steroids)

Renal syndromes (uremia, nephrotic)

Hepatic: Hepatoma, hepatitis, PBC -- primary biliary cirrhosis

Immunologic mechanisms (Mult. Myeloma, SLE)

Drug related (thiazides, beta blockers, tamoxifen, cyclosporine)

acromegaly, lipodystrophy, porphyria

1. Chronic Endothel disfunction/injury
2. Lipoproteins (LDL, VLDL) and lipids gain entry into subendothelium and accumulate.
3. lipoproteins are oxidized!!!
4. Monocytes and plts adhere, monocytes migrate into the intima to eliminate the lipids...become foam cells.
5. signals from macrophages and endothelial cells cause smooth muscle cells to migrate and proliferate in the intima
6. This migration and proliferation cycle continues

Hyperlipidemia

smoking

hypertension

Immune attack

Disturbed blood flow (especially turbulent flow)

toxins

elevated homocysteine

Cytotoxic to endothelial cells and smooth muscle cells

They are chemotactic for monocytes (exacerbating the inflammation), but once in the intima these oxidized LDLs inhibit macrophage mobility out of the tissues.

They stimulate the release of growth factors and cytokines

PDGF, platelet derived growth factor

Released by smooth muscle cells that have invaded the intima in response to signals from macrophages.

Like macrophages, smooth muscle cells take up lipids and cause ECM deposition

What are the consequences of Atherosclerosis?

Narrowed lumen -- limits flow, reversible ischemia, increased demand for blood

Thrombosis -- may occlude the vessel (infarct), sudden and severe.

Generates emboli

Weakens the vessel wall -- aneurysm

What is Hyaline Arteriosclerosis?

A homogenous thickening of arteriolar walls.

It is seen in older people, diabetics. It's more generalized in HTN.

A major component of benign nephrosclerosis

What is Hyperplastic Arteriosclerosis?

This is the "onion skin" that represents a laminar thickening of the vessel walls caused by overproliferation of smooth muscle.

It is often seen in acute elevations or severe HTN "malignant HTN"

Vasculitides (a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels.^[2] Both arteries and veins are affected.)

an aneurysm is a dilation of a blood vessel.

True aneurysm is when the blood producing the dilation is bounded by all 3 portions of the vessel wall (a patent bulge)

False aneurism is a breach in the vessel wall that doesn't penetrate the entire thickness and thus dilates less than 3 layers. The blood reenters the vessel and causes a vascular hematoma.

What is the measurement of an aneurysm that represents a greater then 25% chance of rupture if uncorrected surgically?

Where do Abdominal aneurisms typically occur?

6cm.

Abdominal aneurysms typically occur between the renal arteries and aortic birfurcation into the right and left common iliacs.

What substance causes endothelial cell activation, promotes thrombosis, and increases leukocyte adherence in atheromas?

It can be used as an independent predictor of cardiovascular risk among healty people.

Hint: it's a normal Acute phase reactant

C-Reactive Protein

CRP

________, caused by the spirochete treponema pallidum, can lead to specific aneurysms (_________, or Leutic aneurysms).

These have a typical __________ appearance and can be predictable seen on the _________ and ______ of the aorta.

Symptoms of this condition include:

Syphilis

syphilitic

tree bark

ascending aorta, arch

inflammation of the vasa vasorum leading to obliterative endarteritis; ischemic injury to the aortic media, Left ventricular insufficiency leading to overload and hypertrophy (cor bovinum), impingement on thoracic organs and blood vessels (ex. brachiocephalic)

A _____________ is an accumulation of blood along laminar planes in the aortic media. Rupture can lead to bleed out death in minutes.

This process mainly occurs in two general groups of patients. What are these groups.

Aortic dissection

Occurs mainly in :

1. Men 40-60 y.o. who are hypertensive (non specific histological changes)

2. People with connective tissue disorders such as Marfans syndrome. Marked elastic tissue fragmentation and disruption with cystic/clefted spaces containing amorphous ECM ---->cystic medial degeneration

How does an Aortic dissection classically present?

Block/board-type question:

What is the most common vasculitis seen in adults?

What is the most common vasculitis seen in children?

adults -- Temporal arteritis

Children -- Henock-Schonlein Purpura

What are some possible pathogeneses of Vasculitis?

Infection: Viral, Rickettsial (rocky mountain spotted fever/lyme disease), spirochetal (syphilis), fungal, bacterial

Trauma/toxins

Noninfectious: Immunologic injury (ex. type II, goodpastures; type III, SLE; Type 4, transplant rejection -- ring of infiltration; ANCA associated, wegeners, churg-Strauss, microscopic polyangiitis)

Vasculitis can be classified based on the _____ of the vessels involved.

Give some examples of vasculitis that can be categorized under these headings.

Vessel size classification

Large Vessel:

Giant cell (temporal) Arteritis, Takayasu's

Medium Vessel:

Polyarteritis Nodosa, Kawasaki Disease

Small Vessel:

Wegeners, Churg-Strauss, Microscopic Polyangiitis, Henoch-Schonlein Purpura (most common vasculitis in children)

Giant Cell Vasculitis AKA __________

What are it's characteristics?

Temporal Vasculitis

(most common vasculitis in adults)

1. Usually occurs in older patients
2. Flu-like presentation, severe headache
3. Granulomatous inflammation
4. Affects the temporal arteries and can cause point tenderness and blindness.

Takayasu's

What are its characteristics and in what way might it be similar to Temporal vasculitis?

1. Typically seen in youger patients (prediliction for women and japanese)
2. Presents as a "pulseless" disease...weak pulses in the upper extremitites.
3. Defects (similar to the blindness caused by Temporal)
4. Granulomatous inflammation (similar to Temporal)
5. Affects the Aorta and its major branches (carotic, renal, coronary)

Polyarteritis Nodosa

What is the Key Association to pair PN with?

1. Medium vessels, but may involve smaller vessels -- NEVER arterioles
2. The disease is segmental, sharply demarcated fibrinosed areas with infliction and often secondary thromboses --->distall ischemia
3. Acute, healing, and healed lesions can be seen concurrently
4. All ages affected: fever, malaise, weight loss
5. OFTEN ASSOCIATED WITH HEPATITIS B 
6. Can affect Kidneys (NO GLOMERULAR NEPHRITIS), GI, Muscles, but not the lungs usually

Kawasaki's Disease

Otherwise known as _____________

What are it's characteristics?

Mucocutaneous LN (lymph node) Disease

Involves large, medium, and small arteries

1. Acute illness of children and infants
2. immunoregulatory disturbances
3. Endemic in Japan
4. Clinically

• Fever, lymphadenopathy, skin rash, oral/conjunctival erythema, CORONARY ARTERITIS (20%)
• Lesions Similar to P. Nodosa.

ANCA

What is this acronym and what is it especially helpful with diagnosing and monitoring?

Antineutrophil Cytoplasmic Antibodies

Helpful in pts with SMALL vessel vasculitis

correlates with the active disease and disease severity.

Demonstrated with Immunofluorescence assays

What are the two types of ANCA?

C-ANCA: cytoplasmic, anti-proteinase 3)

P-ANCA: Perinuclear, anti-myeloperoxidase

What are the Small Vessel Vasculitides associated with ANCA?

Wegeners (C-ANCA in 90%)

Microscopic Polyangiitis (P-ANCA)

Churg-Strauss (eosinophil rich) [P-ANCA]

What are the small vessel vasculitides associated with immune comlexes?

Henoch-Shonlein Purpura

Immune comples Glomerulonephritis

Cryoglobulinemia

Graft Rejection

SLE/RA

Microscopic Polyangiitis

AKA?

characteristics

AKA: Polyarteritis, Leukocytoclastic Vasculitis

All lesions are in the same stage, involving the small vessels

"Palpable Purpura from the Polyangitis"

Involves Kidney and Lung (recall: Polyarteritis Nodosa doesn't involve the lungs)

P-ANCA

Neutrophils in whole and fragmented forms infiltrating vessel walls and causing fibrinoid damage.

Churg-Strauss (gezhunteit!)

AKA?

Characteristics?

AKA: Allergic Angiiitis

Necrotizing vasculitis + Granulomas + eosinophils

Strong association with allergic Rhinitis and bronchial asthma, often with perifpheral eosinophilia

P-ANCA in 50% of cases

Wegener Granulomatosis

What is the "triad"?

small vessel vasculitis.

presents with the triad of:

1.Necrotizing granulomas of upper resp. tract, lower resp. tract, or both.

2. Necrotizing granulomatous vasculitis (esp. lungs and upper airway)

3. Renal Desease (with glomerulonephritis)

Males in their 40s

C-ANCA in majority (easy because the other two present with P-ANCA)

Henoch-Shonlein Purpura

Characteristics?

Most common vasculitis in children

Not ANCA associated

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

Multisystem -- skin, gut, kidney, arthritis

Palpable Purpura -- give the kids something to play with, typically on buttocks and lower extremeties

Hematuria and Glomerulonephritis

Polyarthritis

Thromboangiitis Obliterans

AKA?

Characteristics?

AKA: Buerger Disease

Segmental Thrombosing acute and chronic inflamm of medium/small arteries AND veins in the extremities

Usually men <35 who smoke -- apparently it's painful

Arterial neutrophilic infiltrates with thrombi, giant cells, and 2ndary involvement of adjacent vein

May lead to Gangrene

Two connective tissue diseases associated with small vessel vasculitis?

You'll have to recall type 3 Hypersensitivities

SLE

Rheumatoid Arthritis

Raynaud Disease/Phenomenon

Describe the disease vs the Phenomenon

What colorful description can help you recognize Raynaud's?

Disease:

Paroxysmal pallor/cyanosis of fingertips or toes.

Typically occurs in young women, secondary to vasospasm of small arteries/arterioles

exaggerated vasomotor response to cold/stress

Phenomenon:

Extremity arterial insufficiency secondary to arterial narrowing due to other conditions/diseases (ex. CREST)

White-Blue-Red, the appearance of the extremity from the tips toward the body

Varicose Veins

Thrombophlebitis

Varicose Veins

What is the cause of these often age-associated issues?

Abnormally dilated, tortuous veins -- especially in Lupus Erythematosis

secondary to chronically elevated BP

Venous valves become incompetent. Ulcers and stasis dermatitis often develops.

Luminal thrombosis is common but embolisms from these are not

Thrombophlebitis

Describe it, please.

A venous inflammation. An interchangeable term is Phlebothrombosis.

Deep Vein Thrombosis often leads to pulmonary embolism. DVT is the most common type

Trousseau Syndrome involves multiple venous thrombi in the setting of malignancy. These thrombi often travel

Hemangioma

This is a form of Vascular __________.

What are the characteristics?

Vascular Neoplasm

This represents 7% of all benign tumors in children (very common)

This is an overproliferation of surface capillaries. It is most common in the skin and mucus membranes.

Juvenile type

Cavernous type

Pyougenic Granuloma type

Juvenile type hemangioma

AKA?

Discuss

Also known as a Strawberry Hemangioma

Present at birth.

It grows rapidly, but after a few years is self-limiting and involutes (usually by age 7), leaving narry a mark behind. More of a nuisance and eye sore than anything.

Large, cavernous vascular channels. They do not contain tissues from the organ they inhabit. Usually benign neoplasms but can be dangerous in certain tissues (liver and CNS).

They may be seen in von Hippel Lindau ( a rare, autosomal dominant genetic condition^[1]:555 in which hemangioblastomas are found in the cerebellum, spinal cord, and retina)

Pyogenic Granuloma

AKA?

Tell me about it

AKA: Lobular Capillary Hemangioma

An often ulcerated hemangioma. A polyploid variant of the hemangiomas. Often seen after trauma or pregnancy.

According to Dr. pedia, it's mainly an oral hemangioma. Don't let the name throw you, it is not a true granuloma

Kaposi's Sarcoma -- an intermidiate grade ____________ of blood vessels.

What are the 4 forms?

Intermediate grade malignancy

1. Chronic/classic/European -- older men of eastern european descent. Red-Purple plaques of LE. Skin only

2. AIDS-related -- Lesions anywhere in skin/oral mucosa/viscera

3. Lymphadenopathic/African -- Young men in equatorial Africa. Restricted to Lymph nodes. It is aggressive.

4. Transplant associated -- cutaneous and visceral involvement. Lesions may regress with discontinuation of immunosuppression.

All four types of Kaposi's sarcoma (chronic/classic/european; AIDs-related; Lymphadenopathic/African;transplant-associated) progress through the same 3 stages. What are they?

What infection is also common to all the types?

Patch (smooth), Plaque (raised and palpable), Nodular (even more elevated than plaque)

The Blood vessels are spindle shaped rather than round, helping to create the palpable masses. Plasma cells may be found.

All types show infection with Human Herpes Virus 8 (HHV8)

Angiosarcoma

This is a malignant neoplasm of the blood vessels.

It commonly starts in the skin.

It has rare hepatic involvement -- Associated with exposure to Polyvinylchlorides (PVC), Arsenic, thorotrast (was used as a radiocontrast agent in medical radiography in the 1930s and 1940s)

It can show up in breast cancer patients 10 years post mastectomy

It is very aggressive!