Vessels notes Normal anatomy - endothelium - permeable to water and small inorganic forms - Weibel-Palade bodies - makes - prostacyclin - to keep surface slippery; Von Willebrand's factor; endothelin (a vostconstrictor); endothelial-derived relaxation factor - vascular smooth muscle - LDL receptors Birth defects involving vessels - berry aneurysms and arteriovenous malformations - AV malformations involve an abnormal communication between a large artery and a large vein; the problem is shunting of the blood away from the territory which sould be supplied by the artery Atherosclerosis - causes harm by - 1) occluding arteries slowly over time; 2) occluding arteries suddenly by rupture of plaques or hemorrhages into plaques; 3) weakening the walls of arteries - stereotyped response to injury featuring the accumulation of cholesterol-rich fat in the intima of the large and medium-sized arteries of the body - these masses form plaques or artheromas - the cells have great appetite for LDL cholesterol; these cells accumulate lipid and damage their neighbor - risk factors 1) high levels of LDL cholesterol; your LDL is a reflection of your heredity, your diet, and your exercise habits 2) cigaret smoking - damages the intima 3) high blood pressure - which damages the intima 4) diabetes - most work right now focuses on advanced glycosylation end-products - proteins that have been enzymatically glycosylated 5) lack of exercise 6) variety of biochemical lesions 7) other heredity - familial hypercholesteremia - defective B-100 receptor - lipoprotein A allele Lp(s2) is an extremely potent risk factor for coronary artery atherosclerosis 8) low HDL-3 and HDL-2 - both supposedly to keep LDL from binding to plaques - artherosclerosis is accellerated by - previous radiation to an artery, arteries in transplanted hearts, vein grafts in coronary bypass surgery, coranary arteries after angioplasty, situations in which the walls of arteries are burdened with immune complexes - in these situations, endothelial damage and thrombosis appear to be critical - the innocent precursors - fatty streaks - masses of lipid-rich foam cells in the intima - LDL damages endothelium - excess cholesterol makes endothelial cell membrane brittle and prone to crack as the arteries pulsate - LDL makes platelets stick to endothelium too easily - fatty streaks result from macrophages taking up LDL cholesterol, but the LDL must first be altered to oxidized LDL taken up by an exotic receptor on the macrophage surface - oxidized LDL is chemotactic for macrophages - the timb bombs - fibrous plaques - fibrous plaque - masses of cholesterol-rich cells with an overlying fibrous cap; there may be dystrophic calcification, extensive fibrosis and/or smooth muscle hyperplasia in the plaque, and some calcification - cholesterol cells appear as foam cells - when they die they will be cholesterol needles and grumous debris - they increase centrifugally inthe aorta - especially common in bifurcations - the killers - complicated plaques 1) the surface of the plaque becomes damaged, resulting in thrombus formation - the thrombus can embolize if the artery is large, or plug the lumen if the artery is small - the thrombus is more likely to be incorporated into the plaque, making it grow - endothelial damage alone might result from high LDL, a virus, or shear forces of flowing blood - cracking fissuring of the fibrous cap leads to deposition of at least a platelet layer, and often a real thrombus - if the injury reaches the media, the clotting cascade will surely be activated, fibrosis will occur 2) the fibrous cap cracks, discharging grumous debris into the lumen - this can result in embolization if the artery is large, or thrombosis 3) one of the weak little arteries that develops in the plaque bursts, ballooning the roof of the plaque against the opposite wall of a small artery 4) the plaque deprives the inner media of its nutrients, causing it to weaken and balloon out (aneurysm) - it's reversible - artherosclerotic lesions can and do regress Monckenberg's medial calcific sclerosis - dystrophic calcification of the media of arteries, typically in older adults - this is a common, banal, pretty much harmless process; at worst, it can widen one's pulse pressure, or make radial artery blood-gas sticks difficult and hazzardous Arteriolar sclerosis - arteriolosclerosis - two processes which narrow the lumens of the small arteries and arterioles in some or all of the body 1) hyaline arteriolar sclerosis - slow buildup of basement-membrane type material, eventually obliterating the cellular structure of the wall and narrowing the lumen - causes are - prolonged high blood pressure, prolonged hyperglycemia, radiation injury 2) hyperplastic arteriolar sclerosis - concentric, often rapid proliferation of the intimal cells - causes - malignant hypertension, bad pulmonary hypertension, scleroderma, hemolytic-uremic syndrome - all of these processes do damage to the intima of vessels, which presumably undergo hyperplasia The vasculitis family 1) Polyarteritis nodosa - due to hepatitis B infection, anti-myeloperoxidase disease, or idiopathic - important cause of infarcts anywhere in the body except lung 2) Leukocytoclastic vasculitis - type III immune injury of the venules; infarcts and serious damage are rare - refers to dead neutrophils lying about, visible as nuclear dust - mostly from medicines, less common are from cryoglobulinemia, lupus, and antigenemia of HBV and malignancy 3) Werner's granulomatosis - anti-proteinase 3 disease - lung cavities, segmental necrotizing glomerulonephritis with cresents, and vanishing nose, all with granulomas 4) Temporal arteritis - giant cell arteritis - a disease of older adults - macrophages become angry with the internal elastic membrane of the arteries of the external carotid system - jaw elucidation is a picturesque syndrome, but sudden blindness isn't funny - many also suffer from weakness of the muscles - polymyalgia rheumatica - prove diagnosis with a temporal artery biopsy 5) Takayasu's pulsemess disease - aortic arch disease - aortic arch and its great branches thicken and their ostia become stenotic, strangling off blood flow to the upper part of the body - granulomas, lymphocytes, plasma cells, and so forth, in addition to fibrosis and contraction 6) Kawasaki's disease - mucocutaneous lymphoid syndrome - resembles polyarteritis nodosa histologically but occurs in babies and toddlers, mostly of Japanese ancestry - rash on the skin and mucosal surfaces, enlarged lymph nodes, etc. - coronary vasculitis, which causes MIs - healing can produce coronary aneurysms - links to rug and carpet cleaning in the previous month 7) Buerger's disease - thromboangiitis obliterans - disease of young big-time smokers - small neurovascular bundles in the extremities become inflamed and undergo thrombosis - can lose fingers 8) Infectious arteritis - rickettsial disease, syphilis, septic emboli, walls of abscesses, and a host of others - a mycotic aneurysm is a spot at a branch point of an artery where a septic embolus has lodged and set up an infection, weakening the wall 9) Raynaud's disease & phenomenon - spasm and occlusion of the arteries supplying the fingers, which turn white, the red, then blue - triggered by cold weather - scleroderma patients and some others have this process greatly exacerbated by hyperplastic arteriolar sclerosis in the digital arteries Aortic aneurysms - atherosclerosis usually produces aneurysms distally in the aorta, above the level of the iliacs - patients may complain of back pain - aneurysms are always lined by thrombus which sometimes embolizes - iliac aneurysms are also common - basilar artery aneurysms seldom rupture but may compress important things - syphilis causes ischemic damage to the walls of the arteries and is famous for causing proximal aneurysms which rupture impressively - dissecting hematoma is blood which ahs entered the wall of the aorta and is following a weak plane - this catastrophe results in progressive compromise of arteries, backwards rupture damaging the aortic valve and/or ostia, or further backwards rupture into the pericardial sac or pleural space - marfan types are more prone to this lesion Veins - vericose veins - a self-perpetuating process caused by loss of competency in leg vein valves and support structures - can see hemosiderin stasis pigmentation and/or ischemic stasis ulcers - thrombi here very seldom embolize - thrombophlebitis - trombone fleabites - thrombosis of a deep vein - usually inflammation - variants include milk leg, Budd-Chiari syndrome, and dural sinus thrombosis - Trousseau's migratory thrombophlebitis affects first one vein, then another - cause is usually cancer of the pancreas, less often another adenocarcinoma - superior vena cava syndrome - from occlusion, usually from extrinsic compression by lung cancer - patients have dusky skin in the head, upper extremities, and upper chest - inferior vena cava syndrome - from occlusion, usually by cancer in para-aortic lymph nodes; patients have dusky lower bodies and unusual patterns of collateral circulation Lymphatics - lymphangitis - inflammation of lymphatics, usually by a bacterium that's good at invading them; you'll see red stripes running along an extremity - lymphedema - compromise of lymphatic draining of the extremities and/or genitalia - most important causes are cancer of the cervix, filariasis, iatrogenic, autosomal dominant, or idiopathic - if there's hyperplasia of the overlying epidermis, it's elephantiasis Tumors of blood vessels - hemangiomas - mostly hamartomas - capillary hemangiomas and cavernous hemangiomas are common in the skin - stork bites usually involute after a few years, while cherry angiomas of the skin start popping up after age 20 or so - port-wine stain can be treated by laser; a hemangioma in the meninges, generally with an overlying port-wine stain in the V1 areais Strurge-Weber - pyogenic granuloma pops up in the gums of pregnant ladies, or in the skin of anybody - large hemangiomas can consume a person's platelets, the serious Kasabach-Merritt syndrome - Von hippel Lindau anti-oncogene deletion syndrome was recently cloned; it features the most troublesome hemangiomas in all of medicine, as well as renal cell carcinoma - glomangiomas - painful tumors of the smooth muscle of the vestigial human glomus organs, little thermoregulatory left-overs from mammalian evolution and found in the fingertips, toes, and coccyx - telangiectasias - dilatation of the ends of little vessels - Osler-Weber-Rendu telangiectasias results from an autosomal trait - patients have little vascular malformations along their whole GI tract ; these are prone to bleed - the drinker's liver spider is a centrally dialted artery supplying several little arterioles which blanch when the spider's body is pressed - cancers of the blood vessels - confirm the diagnosis using immunostains for factor VIII or by finding Weibel-Palade bodies in the endothelium on electron microscopy - hemangioendotheliomas are low-grade cancers of endothelium; they makes little vessels - angiosarcomas - a host of aggressive cancers; best-known is epidemic hepatic angiosarcoma, caused by exposure to vinyl chloride or thorotrast contrast medium - hemangiopericytomas - low grade cancer of the pericytes; the tumor cells interlace with vessels, beautifully demonstrated in reticulin-stained preparations - Kaposi's sarcoma - the business cell is endothelium, and it can spread and choke off the viscera - the cause is newly-discovered herpes virus - classic American Kaposi's of hte pre-AIDS era mostly involved the legs of older men, and seldom caused major problems - epidemic non-AIDS related Kaposi's is a disease mostly affecting young men in central Africa; it's more aggressive than classic Kaposi's, but not so much as in AIDS-related Kaposi's - lymphangiomas - hamartomas - the best-known is cystic hygroma of the necks of babies - lymphangiosarcomas - cancers of lymphatics, generally arising in lymphedema or after exposure to radiation