Topics B13-15. Cardio 4: Vasculitis, Diseases of Veins and Lymphatics, Tumors and Tumor-like Conditions of Heart/Vessels

Question 1

Non-Infectious Vasculitis: what are the 4 types of pathogenesis from lecture?

Answer 1

1. Circulatory Immune Complexes: attach to vessel wall based on size and charge, activate complement to cause lysis and leukocyte release of ROS. Usually occurs post-infection, but also autoimmune diseases or drug hypersensitivity (haptens)
2. Anti-neutrophil Cytoplasmic Antibodies (ANCA) - will have its own card
3. Anti-Endothelium Antibodies. Occurs in Kawasaki disease
4. T-cell mediated: Granulomatous reaction

Question 2

What are anti-neutrophil cytoplasmic antibodies (ANCA)?

What are the 2 examples of them that we should know?

Answer 2

Antibodies that react with neutrophil cytoplasmic agents, mainly enzymes. They serve as markers for diseases - the type of ANCA is characteristic for specific types of disease. ANCAs can directly activate neutrophils to release their ROS and enzymes, causing inflammation / vasculitis

Types:

1. p-ANCA: Anti-myeloperoxidase. Occurs in PAN: polyarteritis nodosa (at least according to Matolcsy it is, but in reality he is confusing it with microscopic polyangiitis and the others in the department have said that they are afraid to correct him)
2. c-ANCA: anti-proteinase3, part of neutrophil granules. Seen in Wegener granulomatous

Question 3

How are the 3 types of vasculitis classified?

will list examples of each kind in the answer card too

Answer 3

By size:
1. Large Vessel Vasculitis: Giant Cell (Temporal) arteritis, Takayasu arteritis

2. Middle-size Vasculitis: Polyarteritis Nodosa (PAN), Kawasaki Arteritis
3. Small Vessel Vasculitis: Leukoplastic Hypersensitive Vasculitis/Arteritis, Wegener granulomatous, Buerger disease

Question 4

What are the major features of Giant Cell (Temporal) Arteritis?
Who normally gets it? What are their symptoms?
What is the therapy?

Answer 4

Features: affects mostly the “temporal” region of the head, temporal artery but also vertebral and opthalmic. Has chronic granulomatous (T cell mediated) reaction around vessels creating shortage of blood supply. Appears segmental: has lesion, then normal part, then lesion, and so on - important in biopsy. Affects large arteries.

Normally affects women > 30 years old. Get headaches, redness around temporal artery, may have vision problems, fatigue, weight loss, fever, and ischemic lesions of the brain.

Therapy is steroid treatment, usually responds well.

Question 5

What are the major features of Takayasu Arteritis?

Who normally gets it?

Answer 5

Major feature: “pulseless disease” - weak pulse due to aortic arch narrowing. Also likely to lose vision because it’s so sensitive to blood supply. Also have a granulomatous reaction in endothelium. Affects large arteries.

Pretty much exclusively exists in Asia, ages 15-30.

Question 6

What are the major features of Polyarteritis Nodosa (PAN)?
What are the major clinical consequences?
Which ANCA is it characterized by?
What is the therapy?

Answer 6

“Segmental Necrotizing Vasculitis” - segments with fibrinoid necrosis. Obliterates one side, and the other side has weak wall that forms aneurysm. In long run, it heals via thrombosis and fibrotic narrowing, making ischemia and atrophy of organs - kidney, GI, brain, liver, heart, spleen. Affects middle and small size arteries.

Most dramatic clinical effect is kidney failure, and necrosis may cause massive hematuria. Others: bleeding GI ulcers, MI, stroke.

Has p-ANCA (again, it actually doesn’t but a lot of people, especially Matolcsy, think it does, so you should mention it on the exam)

Therapy: cytostatic drugs and immunosuppression

Question 7

Kawasaki arteritis: what are the major features and clinical consequences?
Who normally gets it?

Answer 7

Similar to PAN, but it’s in children before age 4. Vasculitis is localized to mucous membranes, skin, and coronary arteries. See MI, GI tract infarcts, and dermal involvement. Affects middle and small arteries.

Rare disease, endemic to Japan

Question 8

Leukocytoclastic Hypersensitive Vasculitis / Arteritis: what is it caused by? What are its main features and clinical consequences?
Which ANCA does it have?
What is the therapy?

Answer 8

Caused by hypersensitive reaction to drugs, e.g. penicillin or other antibiotics, or could be microorganisms. Affects small vessels like capillaries and venules - histologically see leukocytic infiltration with fragmented nuclei (most characteristic feature). Affects the glomeruli and pulmonary capillaries, causing hematuria, proteinuria, and hemoptysis

Has p-ANCA.
Therapy: withdrawal of drug

Question 9

Wegener Granulomatosis: What are its 3 clinical features?

Which ANCA does it have?

Answer 9

3 clinical features: necrotizing vasculitis, granulomas in respiratory tract (upper and lower), glomerulonephritis. Affects small vessels.
Very severe, progressive disease. Leads to rapid kidney failure, pulmonary distress, and shortage of blood supply and ischemia to different organs.

Related to c-ANCA.

Question 10

Thrombangitis Obliterans (Buerger Disease): What is it caused by and the pathogenesis?

What are the main clinical symptoms?

Answer 10

Reaction to direct toxicity of tobacco products on small vessel endothelium of the fingers and hand vasculature. Hypersensitivity causes vasospasm. Get small abscesses in the wall, invaded by neutrophils, and thrombosis occurs in lumen with ischemia.

Clinical features: superficial nodular phlebitis, cold sensitivity, pain, chronic ulcerations. Quitting smoking relieves symptoms.

Question 11

What are the 3 diseases of the veins mentioned in Robbins?

Answer 11

1. Varicose Veins: both of the extremities and ones from portal hypertension, like esophageal varices. Could also mention hemorrhoids or varicocele.
2. Thrombophlebitis and Phlebothrombosis: inflammation that’s due to thrombus formation in the veins, normally the deep veins of the leg
3. Superior and Inferior Vena Cava Syndromes: compression of these great veins, usually from tumor

(#1 and 2 account for >90% of clinical relevant venous diseases)

Question 12

What causes varicose veins? Where do varicose veins of the extremities usually occur?

What are some risks factors that predispose people to varicose veins of the extremities?

Answer 12

Varicose veins are abnormally dilated tortuous veins that result from chronically increased venous pressure and weakened vessel wall. On the extremities, usually affects superficial veins of leg.

Risk factors: Obesity, some genetic predisposition, female gender (probably IVC compression during pregnancy)

Question 13

What are the clinical risks of having varicose veins of the extremities?

Answer 13

• Venous valves become dysfunctional, causing stasis, congestion, edema, pain, and can cause thrombosis (but embolisms from these are very rare)
• Persistent edema is most disabling feature
• Secondary ischemic changes: “stasis dermatitis” and ulcerations
• Poor wound healing, may have more infections

Question 14

What are 2 places that varices appear as a result of portal hypertension?

Also, hemorrhoids?

Answer 14

1. Esophageal varices: most important because ruptures can lead to massive, fatal upper GI bleeding
2. Periumbilical veins: Caput Medusae

Hemorrhoids: prolonged pelvic vascular congestion, associated with pregnancy or straining to defecate. Can also cause bleeding, prone to thrombosis and painful ulceration

Question 15

What is thrombophlebitis?

What are 5 locations that it occurs?

Answer 15

Thrombophlebitis is inflammation resulting from thrombus in a vein.

1. Deep veins of leg: most important one. Major risk is emboli
2. Periprostatic veins in males
3. Pelvic venous plexuses in females
4. Dural sinuses and other large veins in the skull
5. Portal vein (Pyle thrombus): more likely if there are some is some sort of peritonitis or hypercoagulability state. Has risk of bowel ischemia.

Question 16

What can cause DVT (Deep Vein Thrombosis)?

3 answers are listed, but one of them is a general category with several examples

Answer 16

1. Normally seen after prolonged inactivity of the leg: bedrest, long flights, etc.
2. Things associated with increased risk for blood clots: birth control, pregnancy, obesity, inherited defects of coagulation
3. Malignant tumors that cause Trousseau syndrome

Question 17

What are the symptoms of DVT?

What is the major risk?

Answer 17

Symptoms: general inflammation signs like edema, heat, redness, pain.
May also see cyanosis if it’s severe.

However, it’s often asymptomatic. In many cases the first sign is the most important risk: embolism that spreads to the lungs (pulmonary embolism).
Make sure you differentiate it from the superficial vein thrombosis that has low risk for embolism.

Question 18

Does portal vein thrombus that ends up in the liver cause infarction? What is the morphology of it?

Answer 18

It does not cause ischemic infarction, but a sharply-demarcated area of red-blue discoloration (aka “Infarct of Zahn”).

Does not have necrosis, but see hepatocellular atrophy and congestion in distended sinusoids

Question 19

What are 2 specific neoplasms that can cause Superior Vena Cava Syndrome?
And 2 for Inferior Vena Cava Syndrome?

Answer 19

SVCS: Bronchogenic Carcinoma or Mediastinal Lymphoma.

IVCS: Hepatocellular Carcinoma or Renal Cell Carcinoma. These have strong tendency to grow within veins

Question 20

What are the signs and symptoms of Superior Vena Cava Syndrome?

What are the symptoms and risks of Inferior Vena Cava Syndrome?
(it’s completely logical)

Answer 20

SVCS: Dilation of veins of head, neck, arms - associated with cyanosis. Also may have pulmonary vessel compression, causing respiratory distress

IVCS: Lower extremity edema, distension of collateral veins of abdomen, and proteinuria due to renal vein involvement.

Question 21

What are 3 problems in the lymphatic system to mention if you get this topic?

Answer 21

1. Lymphangitis: bacterial invasion of lymph vessels, seen as red, painful subQ streaks.
2. Lymphadenitis: if bacteria also spread to lymph node, these are swollen and tender
3. Lymphedema: can be primary (congenital, maybe part of Milroy disease) or secondary (caused by obstruction)

Question 22

What are some causes of lymphatic obstruction that can lead to secondary / obstructive lymphedema?
(4 answers are listed, but only 2 are really important)

Answer 22

1. Tumors involving lymph channels or nodes
2. Surgical procedures that sever lymph connections (especially know this risk in axillary nodes after mastectomy)
3. Filiarisis
4. Postinflammatory thrombosis and scarring

Question 23

What are 2 potential clinical consequences of chronic lymphedema?

Answer 23

1. Deposition of ECM and fibrosis -> brawny induration or “peau d’orange” of overlying skin. Skin can then be ulcerated
2. Rupture: milky accumulations of lymph on various spaces: chylous ascites, chylothorax, chylopericardium

Question 24

What are 3 tumors that can grow from endothelial cells?

Answer 24

1. Hemangioma (benign)
2. Angiosarcoma (malignant, rare)
3. Lymphangioma (benign)

Question 25

What is the key difference in the morphology of blood vessel tumors when they are benign vs malignant?

Answer 25

Benign: lined by normal endothelial cells, productive obvious vascular channels

Malignant: vessels are disorganized, unclear

Question 26

What are 3 “tumor-like conditions” of the blood vessels?

Answer 26

1. Ectasia: any local dilation of a structure
2. Telangiectasia: Permanent dilation of preexisting small vessels (capillaries, venules, and arterioles). Usually in the skin or mucous membranes.
3. Bacillary Angiomatosis: vascular proliferation in immunocompromised people infected with Bartonella (bacteria causing cat scratch fever)

Question 27

What are 4 examples of either Ectasias or Telangiectasias from Robbins?

Answer 27

1. Nevus flammeus: birthmark, usually on head or neck
2. Port wine stain nevus: a form of nevus flammeus, may indicate other vascular malformations like Sturge-Weber syndrome
3. Spider telangiectasia: appear on upper body, associated with hyperestrogen states like pregnancy or people with liver cirrhosis
4. Hereditary Hemorrhagic Telangiectasia: TGF-β mutation, wide distribution on skin/oral mucosa. Often rupture -> bleeding

Question 28

What is Bacillary Angiomatosis?

What do the lesions look like?

Answer 28

Vascular proliferation in immunocompromised hosts that occurs during Bartonella bacterial infection. The bacteria induces tissue to produce Hypoxia-Inducible rowth Factor (HIF) which drives VEGF production and vascular proliferation

Skin lesions are red papules and nodules or rounded subQ masses.

Question 29

What are 3 benign tumors of blood vessels?

Answer 29

1. Hemangiomas: common in childhood, often appear on liver.
2. Lymphangiomas: similar to hemangioma, just in lymph vessels
3. Glomus tumors: painful tumors that arise from smooth muscle cells of glomus bodies (part of thermoregulatory function). Affects the distal fingers and toes.

Question 30

What type of vascular tumor commonly arises in HIV infection?

What does it look like?

Answer 30

Kaposi Sarcoma: caused by HHV-8 that is not contained due to immunocompromised state. Rarely shows up on non-HIV infected people

Usually appears with multiple red-purple skin plaques or nodules, usually in the distal lower extremities. These progressively increase in size and number, and the plaques may become raised. Usually asymptomatic, only on skin and subcutaneous tissue.

Question 31

What is angiosarcoma?

What are 2 examples of specific angiosarcomas, and their causes?

Answer 31

Malignant neoplasm of endothelium, somewhere on the spectrum of highly differentiated to anaplastic. Begin as small red nodules, become large red-tan to gray-white masses without clear borders. Occurs more often in liver, skin, soft tissue, breasts. Prone to metastases, poor survival rate.

1. Hepatic angiosarcomas are related to pesticides and plastics (PVC).
2. Lymphangiosarcomas may arise from lymphedema as a result of lymph node resection after breast cancer

Question 32

Where do most metastatic-origin heart tumors come from?

Answer 32

In descending order: lung, lymphoma, breast cancer, leukemia, melanoma, liver or colon carcinoma.

Almost all heart tumors are metastatic, very few are primary (originate in the heart)

Question 33

What are the 3 most common and important primary neoplasms of the heart?

Answer 33

1. Angiosarcoma of the heart: only malignant tumor, same morphology as other angiosarcomas
2. Myxoma: connective tissue tumor. Most common primary tumors in adults, usually in left atrium fossa ovalis.
3. Rhabdomyomas: muscle tumor. Most frequent primary tumors of heart in children. Higher frequency in people with TSC1 or TSC2 tumor suppressor gene mutations.

(2 less important ones: Lipomas, Papillary fibroelastomas)

Question 34

What are the major clinical manifestations of cardiac tumors?
(3 listed, the first 2 are more important)

Answer 34

1. Valvular obstruction: “ball-valve”
2. Embolization
3. General signs of fever and malaise from tumor releasing IL-6