Flashcards in Topics B13-15. Cardio 4: Vasculitis, Diseases of Veins and Lymphatics, Tumors and Tumor-like Conditions of Heart/Vessels Deck (34)
Non-Infectious Vasculitis: what are the 4 types of pathogenesis from lecture?
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
What are anti-neutrophil cytoplasmic antibodies (ANCA)?
What are the 2 examples of them that we should know?
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
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
How are the 3 types of vasculitis classified?
(will list examples of each kind in the answer card too)
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
What are the major features of Giant Cell (Temporal) Arteritis?
Who normally gets it? What are their symptoms?
What is the therapy?
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.
What are the major features of Takayasu Arteritis?
Who normally gets it?
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.
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?
"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
Kawasaki arteritis: what are the major features and clinical consequences?
Who normally gets it?
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
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?
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
Therapy: withdrawal of drug
Wegener Granulomatosis: What are its 3 clinical features?
Which ANCA does it have?
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.
Thrombangitis Obliterans (Buerger Disease): What is it caused by and the pathogenesis?
What are the main clinical symptoms?
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.
What are the 3 diseases of the veins mentioned in Robbins?
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)
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?
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)
What are the clinical risks of having varicose veins of the extremities?
-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
What are 2 places that varices appear as a result of portal hypertension?
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
What is thrombophlebitis?
What are 5 locations that it occurs?
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.
What can cause DVT (Deep Vein Thrombosis)?
(3 answers are listed, but one of them is a general category with several examples)
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
What are the symptoms of DVT?
What is the major risk?
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.
Does portal vein thrombus that ends up in the liver cause infarction? What is the morphology of it?
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
What are 2 specific neoplasms that can cause Superior Vena Cava Syndrome?
And 2 for Inferior Vena Cava Syndrome?
SVCS: Bronchogenic Carcinoma or Mediastinal Lymphoma.
IVCS: Hepatocellular Carcinoma or Renal Cell Carcinoma. These have strong tendency to grow within veins
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)
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.
What are 3 problems in the lymphatic system to mention if you get this topic?
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)
What are some causes of lymphatic obstruction that can lead to secondary / obstructive lymphedema?
(4 answers are listed, but only 2 are really important)
1. Tumors involving lymph channels or nodes
2. Surgical procedures that sever lymph connections (especially know this risk in axillary nodes after mastectomy)
4. Postinflammatory thrombosis and scarring
What are 2 potential clinical consequences of chronic lymphedema?
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
What are 3 tumors that can grow from endothelial cells?
1. Hemangioma (benign)
2. Angiosarcoma (malignant, rare)
3. Lymphangioma (benign)
What is the key difference in the morphology of blood vessel tumors when they are benign vs malignant?
Benign: lined by normal endothelial cells, productive obvious vascular channels
Malignant: vessels are disorganized, unclear
What are 3 "tumor-like conditions" of the blood vessels?
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)
What are 4 examples of either Ectasias or Telangiectasias from Robbins?
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
What is Bacillary Angiomatosis?
What do the lesions look like?
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.
What are 3 benign tumors of blood vessels?
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.