blood vessels
Terms
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- Define [blood] coagulation
- formation of a [blood] clot as a result of activation of the clotting cascade. It may occur in vitro (artificial environment)
- Define thrombosis and the physiological functions included.
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formation of a blood clot in situ (natural position).
 Blood coagulation
 Platelet adherence and aggregation
 Endothelial cell interactions
 Participation of the monocyte/macrophage system. - Define hemostasis and the physiological functions included.
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arrest of hemorrhage as a response to vascular injury
Tightly controlled by a network of activating/inactivating enzymes and cofactors, derived from different cells and tissues, some of which are circulating and some of which are locally produced.
 Blood coagulation
 Platelet adherence
 Endothelial cell interactions
 Participation of the monocyte/macrophage system
 Fibrinolysis - The coagulation process requires....
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1. Coagulation factors (proteins): manufactured by the liver.
2. Ca++: is available in the blood and from intracellular sources.
3. Phospholipids: components of cellular and platelet membranes. They provide a surface upon which the chemical reactions of coagulation can take place. - Describe the 2 coagulation pathways.
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1. INTRINSIC PATHWAY: requires only elements (clotting factors, Ca++, platelet surface etc.) found within, or intrinsic to the vascular system.
2. EXTRINSIC PATHWAY: requires Tissue Factor (tissue thromboplastin), a substance which is “extrinsic to,†or not normally circulating in the vessel. Tissue Factor is released when the vessel wall is RUPTURED. - Platelet Adherence is facilitated by...
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collagen
van Willebrand factor by the endothelial cells. - Platelet aggregation is enhanced by...
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ADP
thromboxane A2
Thrombin - Definition of atherosclerosis.
- disease of large- and medium-sized arteries that results in progressive accumulation within the intima of smooth muscle cells, lipids, and connective tissue. Continued growth of the lesion encroaches on other layers of the arterial wall and narrows the lumen
- Pathogenesis/Pathology of atherosclerosis
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1. Proliferation of smooth muscle cells, accumulation of lipids (LDL), and inclusion of macrophages, lymphocytes, and connective tissue.
2. Disruption of the endothelium, which initially originates the deposition of platelets.
3. More severe disruption of the endothelium causes thrombosis and proliferation of small capillaries within the intima, which vascularize the plaque (“vasa plaquorumâ€) --> OCCLUSION OF THE ARTERY. - Hypotheses to explain the origin of atherosclerosis: (6)
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1. INSUDATION HYPOTHESIS: inclusion of plasma lipoproteins (especially LDL) from the bloodstream.
2. INTIMAL CELL MASS HYPOTHESIS: accumulation of smooth muscle cells. Intimal cell masses.
3. MONOCLONAL HYPOTHESIS: migration and mitosis of 1 smooth muscle cell, that proliferate due to mutagens, viral infections, etc.
4. ENCRUSTATION HYPOTHESIS: formation of small mural thrombi.
5. HEMODYNAMIC HYPOTHESIS: factors like blood pressure, turbulence, and shear forces.
6. REACTION TO INJURY HYPOTHESIS**: injury (mechanical, infection, etc.) of the blood vessel, which provokes the accumulation of platelets, lymphocytes, and macrophages. These cells (and the endothelial cells) secrete PDGF (platelet derived growth factor, a potent chemotactic and mitogen for smooth muscle cells) and engulf lipids. - What are the 2 types of initial lesions?
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fatty streaks
intimal cell masses - describe fatty streaks
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⬢ Flat or slightly elevated lesions that contain accumulations of intracellular and extracellular lipid in the intima.
⬢ Fat is accumulated in the macrophages and smooth muscle cells.
⬢ They are found in young children as well as adults.
⬢ Distribution does not correspond to the lesions. - describe intimal cell masses
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⬢ White, thickened areas at branch points in the arterial tree, containing smooth muscle cells and connective tissue, but NO LIPID.
⬢ Location correlates well with the one of later atherosclerotic lesions.
⬢ However, they do not necessarily progress to atherosclerotic lesions. - What is the characteristic atherosclerotic lesion?
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Fibro-fatty plaque consisting of:
1. Atheroma (core): lipid-filled macrophages and necrotic smooth muscle cells debris.
2. Fibrous cap: macrophages, lymphocytes, and endothelial cells, and connective tissue (smooth muscle cells, which produce collagen, elastin, and glycosaminoglycans, cause thickening of the intima). - Complicated plaques
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Responsible for impairing blood flow.
• Thrombosis, on and within the fibrous cap.
• Neovascularization of the cap and shoulders (“vasa plaquorumâ€)
• Thinning of the underlying media.
• Calcification
• Ulceration - Complications of atherosclerosis.
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main targets: aorta, coronary, cerebral systems
1. Myocardial infarction (Occlusive Coronary Disease)
2. Cerebral infarction (stroke)
3. Gangrene
4. Aneurysm Formation
5. Chronic vessel stenosis (chronic narrowing of the vessel)
6. Organ ischemia (blood supply interference) and atrophy
7. Embolism (thrombus detach and lodge in a distal vessel).
1-4 above are “ACUTE OCCLUSION†& 5-7 above are “CHRONIC ATHEROSCLEROSIS†- Risk Factors of atherosclerosis
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Any factor associated with doubling in the incidence of ischemic heart disease is defined as being a risk factor.
1. Hypertension
2. Blood cholesterol level (LDL “bad cholesterol,†HDL “good cholesterolâ€)
3. Cigarette smoking
4. Increasing age and male sex
5. Physical inactivity and stressful life patterns
6. Diabetes (induces hypercholesterolemia)
7. Genetic defects that produce dysfunction in lipoprotein metabolism (dyslipoproteinemias)
*Familiar hypercholesterolemia (mutations in the LDL receptor). - Definition of hypertension.
- Systolic pressure greater than 160 mm Hg, a diastolic pressure greater than 90 mm Hg, or both. It is a major risk factor for a variety of cardiovascular disorders. It usually affects SMALL muscular arteries and arterioles.
- Pathogenesis of hypertension.
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Imbalance in mechanisms controlling blood pressure, which are:
1. Cardiac output
2. Peripheral resistance - Control of hypertension (3)
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1. Diuretics
2. ACE Inhibitors
3. alpha-adrenergic or beta-adrenergic blocking agents (alpha-blockers and beta-blockers) - Pathology of hypertension.
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ARTERIOSCLEROSIS/ARTERIOLOSCLEROSIS
Definition: Refers to vascular changes characterized by thickening and loss of elasticity of arterial walls. When affects ARTERIOLES, it is called arterioLOsclerosis. - Types of hypertensive (arteriosclerotic) lesions
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1) benign (hyaline) arteriosclerosis
2) malignant (accelerated) hypertension - benign (hyaline) arteriosclerosis
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Definition: mild, chronic hypertension, where the major change is a variable increase in thickness of the vessel walls.
Pathology:
⬢ Deposition of basement membrane material and accumulation of plasma proteins.
⬢ Common in diabetes. - malignant (accelerated) hypertension
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Definition: situation in which elevated blood pressure results in rapidly progressive vascular compromise, with the onset of symptomatic disease of the brain, heart, or kidney.
Pathology:
⬢ Necrosis of smooth muscle and endothelial cells with deposition of plasma proteins in the walls of the vessels (fibrinoid necrosis). - Monckeberg Medial Sclerosis
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Definition: Degenerative calcification of the media of large- and medium-size muscular arteries, which occurs principally in older persons.
⬢ Cause is unknown, but it is distinct from atherosclerosis or arteriosclerosis.
⬢ Ordinarily, does not lead to any clinical disorder (calcific deposits do not narrow the lumen).
⬢ Vessels of extremities are most often involved (femoral, tibial, radial, etc.) - Raynaud Phenomenon
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Definition: Intermittent, bilateral attacks of ischemia in the fingers or toes, and sometimes in the ears or nose, secondary to intense arterial vasospasm in the skin.
⬢ Characterized by severe pallor, and is often accompanied by paresthesias and pain. Symptoms are precipitated by cold or emotional stimuli, and they are relieved by heat.
⬢ May occur as an isolated disorder or as prominent feature of a number of systemic diseases of the connective tissue (scleroderma). - Definition of aneurysm.
- Arterial aneurysms are localized dilatations of blood vessels caused by a congenital or acquired weakness in the media. The wall of an aneurysm is formed by the stretched remnants of the arterial wall. Their incidence tends to increase with age
- Morphologically, aneurysms can be classified as:
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1. Fusiform Aneurysm: an ovoid swelling parallel to the long axis of the vessel.
2. Saccular Aneurysm: a bubble-like outpouching of the arterial wall.
3. Dissecting Aneurysm: a dissecting hematoma in which hemorrhage into the media separates the layers of the vascular wall by a column of blood.
4. Arteriovenous Aneurysm: a direct communication between an artery and a vein. - Definition of atherosclerotic aneurysms.
- aneurysms of the abdominal aorta and common iliac arteries, which are lined by a raised, ulcerated, and calcified (complicated) atherosclerotic lesion
- Pathology of atherosclerotic aneurysms.
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⬢ Atherosclerosis causes arterial wall thinning through medial destruction secondary to the plaque that originates in the intima. Normal arterial wall may even be totally destroyed and replaced by fibrous tissue.
⬢ Most of them are distal to the renal arteries and proximal to the bifurcation of the aorta.
⬢ Usually fusiform or saccular. - Clinical features of atherosclerotic aneurysms.
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they are the MOST FREQUENT aneurysms, usually developing after the age of 50. More often in MEN, ½ of these patients are HYPERTENSIVE. Many are asymptomatic. They may present with abdominal pain.
Complications: rupture followed by retroperitoneal hemorrhage; ½ the patients die. - Definition of aneurysms of cerebral arteries.
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aneurysms that occur in the cerebral arteries, usually leading to fatal subarachnoid hemorrhage.
The most common is called Berry aneurysm, because it is saccular and resembles a berry attached to a “twig†of the arterial tree - Pathology of aneurysms of cerebral arteries.
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⬢ Berry aneurysms result from a congenital defect in a branch point of the arterial branch.
⬢ They tend to arise at 1 of the branching angles of the Circle of Willis or in 1 of the arterial branches. - CLinical features of aneurysms of cerebral arteries.
- usually fatal by subarachnoid hemorrhage. They are common (found in 2% of postmortem examination). SMOKING and HYPERTENSION are accepted predisposing factors. Although congenital, they are NOT identifiable at birth
- Define dissecting aneurysms.
- dissecting aneurysms refers to the entry of blood into the arterial wall and its extension along the length of the vessel. They often affect the ascending aorta and its major branches (coronary arteries, great vessels of the neck, renal, mesenteric, or iliac arteries).
- Pathology of dissecting aneurysms.
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• Although conventionally termed an aneurysm, it is actually a form of HEMATOMA.
• Caused by defects or weakness in the connective tissue of the media, with loss of muscle fibers, that leads to “spaces†filled with myxoid material. - Clinical features of dissecting aneurysms.
- HYPERTENSION is a major risk factor. MEN are affected more often than women. It can happen at any age, but usually during the 6th and 7th decades. Also occurs during pregnancy. They have fatal consequences, as they often rupture, causing massive hemorrhage
- Define micotic aneurysm.
- Aneurysms that occur as a result of a bacterial infection
- Define syphilitic aneurysms.
- Aneurysms that occur as a result of an onset of syphilis (caused by Treponema Pallidum infection), in its tertiary stage
- Pathology of syphilitic aneurysm.
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⬢ May involve small vessels in any part of the body, but it is clinically most devastating when it affects the aorta.
⬢ Characterized by medial destruction as the result of the inflammatory reaction. - Clinical features of syphilitic aneurysm.
- less common nowadays. Symptoms include difficulties breathing, swallowing, persistent cough, and final rupture of the aneurysm. Most patients die of heart failure
- Definition of vasculitis.
- inflammation and necrosis of blood vessels, including arteries, veins, and capillaries. In most cases, no specific cause is determined
- Pathogenesis of vasculitis (3)
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Vasculitis syndromes usually are caused by:
1. Direct trauma (mechanical trauma, radiation, etc.), or infection (herpesvirus, cytomegaloviruses, parvovirus) of blood vessels.
2. Chronic infection of other organs (chronic hepatitis B virus infection), which causes deposition of antigen-antibody complexes in the blood vessels.
3. Direct attack (autoimmune reaction) against blood vessels by circulating antibodies or inflammatory cells. - Diagnosis of vasculitis.
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Tissue biopsy and ANCA staining:
Serum from many patients with vasculitis contains ANCA antibodies (Anti-neutrophil Cytoplasmic Antibodies) that react with cytoplasmic antigens in neutrophils.
As a diagnostic test, normal neutrophils are placed on a dish, then incubated with a sample of the patient’s serum. Cells are then fixed and complexes can be detected by immunofluorescence.
2 types of staining may be found:
1. p-ANCA: perinuclear staining
2. c-ANCA: cytoplasmic staining - Polyarteritis Nodosa
- acute, necrotizing, systemic vasculitis that affects medium-size and smaller muscular arteries and, occasionally, larger arteries
- Hypersensitivity Angiitis (microscopic polyarteritis)
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broad category of inflammatory vascular lesions thought to represent a response to exogenous substances, such as bacterial products or drugs.
Restricted to the smallest arteries and arterioles.
If confined to the skin is called Cutaneous Vasculitis - Allergic granulomatosis and angiitis (churg-strauss syndrome)
- systemic vasculitis with prominent eosinophilia that occurs in young persons with asthma
- giant cell arteritis (temporal arteritis)
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a focal, chronic, granulomatous inflammation of the temporal arteries.
Most common form of vasculitis.
It can also involve other arteries.
Affects primarily elderly persons - wegener granulomatosis
- systemic, necrotizing vasculitis characterized by granulomatous lesions of the respiratory tract (nose, sinuses, and lungs) and renal glomerular disease
- Takayasu arteritis
- inflammatory disorder of large arteries, classically the aortic arch and its major branches
- kawasaki disease (mucocutaneous lymph node syndrome)
- acute disease of infancy and early childhood characterized clinically by high fever, rash, conjunctival and oral lesions, and lymphadenitis and pathologically by an acute necrotizing vasculitis
- Thromboangiitis obliterans (buerger disease)
- occlusive, inflammatory disease of the small- and medium-size arteries in the distal arms and legs. Almost exclusively occurs in young and middle-aged men who smoke heavily
- Define varicose veins of the legs.
- Varicose veins are enlarged, tortuous blood vessels. Most commonly occur in the saphenous system.
- Pathology of varicose veins of the legs
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⬢ There is both an incompetence of the valves and a dilatation of the vessel.
⬢ Vessel exhibit variations in their thickness. Some areas present dilatation causing thinning of the wall. Other areas present thickening from subintimal fibrosis, thrombosis and hypertrophy of the media.
⬢ Vascular deformities consist of thickening, shortening or elongation and rolling of the cusps. - Risk factors of varicose veins of the legs.
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1. Age: rises with age (50% incidence in persons older that 50 years).
2. Sex: more common in women (specially after pregnancies).
3. Heredity: strong familial predisposition.
4. Posture: Standing up for long periods of time.
5. Obesity: excessive body weight
6. Others: any factor that increases venous pressure in the legs. - Definition of "varicose veins at other sites"
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Enlarged, tortuous blood vessels found in other locations (not legs)
hemorrhoids
esophageal varices
varicocele - Hemorrhoids
- Dilatations of the veins of the rectum and anal canal. The condition is aggravated by constipation and pregnancy. It may also result from venous obstruction by rectal tumors. Painful
- Esophageal varices
- Complication as a result of portal hypertension caused mainly by cirrhosis of the liver. High portal pressure leads to distention of the anastomoses between the portal system and the systemic veins at the lower end of the esophagus. Hemorrhage from these varices is one of the most common causes of death in patients with cirrhosis.
- Varicocele
- Palpable mass in the scrotum formed by varicosities of the pampiniform plexus
- Definition of deep venous thombosis
- Thrombosis of the veins, usually associated with prolonged bed rest or reduced cardiac output. Frequently affects the deep leg veins. They can be a major threat to life because of embolization to the lung (cause of sudden death occurring on ambulation after surgery).
- Phlebothrombosis
- Venous thrombosis in the absence of an initiating infection or inflammation
- THrombophlebitis
- Venous thrombosis secondary to inflammation of small veins, commonly as part of a local reaction to bacterial infection.
- Lymphangitis
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Inflammation of the lymphatic vessels, caused by the entrance of bacteria and inflammatory cells from sites of drainage. Affects predominantly the regional lymph nodes.
Caused specially by Streptococcus. - Lymphatic Obstruction
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Obstruction of the lymphatics caused by
scar tissue
intraluminal tumor cells
plugging with parasites - Types of lymphatic obstruction (4)
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lymphedema: major obstruction
lymphangiectasia: dilatation of lymphatics
elephantiases: grossly enlarged lymphedematous LIMB.
milroy disaese: inherited type of lymphedema present at birth. - Hemangiomas (traditionally called capillary hemangiomas)
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a vascular birthmark of benign tumors.
Congenital neoplasms of uncertain origin, characterized by an increased number of normal or abnormal vessels, resembling capillaries. - Related pathologies of hemangiomas (2)
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⬢ Kasabach-Merritt syndrome: large/giant hemangiomas or diffuse hemangiomatosis throughout the body.
⬢ Pyogenic Granuloma (Lobular Capillary Hemangioma). This polypoid form of capillary hemangioma occurs as a rapidly growing exophytic red nodule attached by a stalk to the skin and gingival or oral mucosa. Pregnancy tumor (granuloma gravidarum) occurs in the gingiva of 1 to 5% of pregnant women and regress after delivery. - What are the 4 characteristics of benign tumors?
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vascular birthmarks
glomus tumor
vascular ectasias
reactive vascular proliferations - What are the 2 types of intermediate-grade tumors?
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Kaposi's sarcoma
Hemangioendothelioma - What are the 2 types of malignant tumors (vascular)?
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angiosarcoma
hemangiopericytoma. - What are the types of vascular malformations (4)?
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1. Capillary malformations (cavernous hemangioma)
2. Venous malformations
3. Lymphatic malformations
4. Arteriovenous malformations - von Hippel-Lindau syndrome (VHL syndrome):
- genetic disease characterized by development of multiple hemangiomas that occur in the cerebellum, brain, retina and kidney.
- Define glomus tumor.
- Benign, exquisitely painful tumor that arises from the modified smooth muscle cells of the glomus body (specialized arteriovenous anastomosis involved in thermoregulation), most commonly affecting the distal regions of the fingers and toes.
- Define vascular ectasias.
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Localized congenital or acquired exaggerations of preexisting vessels (not true neoplasms).
The most common are Nevus Flammeus, Spider Telangiectasia and Hereditary Hemorrhagic Telangiectasia (which affects the oral cavity) - Define reactive vascular proliferations
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The most common is Bacillary Angiomatosis.
Vascular proliferations in the skin, bone, brain and other organs, caused by opportunistic infection of immunocompromised patients with Bartonella. - Define Kaposi's Sarcoma (KS)
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intermediate-grade tumor
Multifocal vascular tumor affecting immunocompromised patients and caused by infection with human herpesvirus 8 (HHV8). - Pathology of KS
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- Affects the skin, oral cavity, lymph nodes, and visceral organs (GI tract specially)
- Characterized by the presence of tortuous blood vessels, erythrocyte filled-vascular spaces and inflammatory infiltrate.
- Infection with HHV8 (or Kaposi’s sarcoma associated herpesvirus, KSHV), is necessary but not sufficient for disease onset. Secondary factors may include immunosuppresion, HIV infection or cytokine release caused by inflammation. - Types of Kaposi's Sarcoma (4)
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Classic: Mediterranean men, lower extremities.
Endemic (african)
transplant-associated (iatrogenic): due to immunosuppresive therapy. infection comes from organ donor.
AIDS-associated: MOST COMMON CANCER in HIV-infected patients-homos. - Define hemangioendothelioma.
- Vascular tumor showing histological features and clinical behavior intermediate between benign hemangiomas and malignant angiosarcomas.
- What are the 2 types of hemangioendotheliomas?
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⬢ Epithelioid hemangioendothelioma
⬢ Spindle cells hemangioendothelioma - Define Angiosarcoma
- Highly malignant endothelial neoplams with structure varying from highly differentiated tumors that resemble hemangiomas to very anaplastic tumors.
- Pathology of angiosarcoma
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- Anywhere, but mostly in the skin, soft tissue, breast, bone, spleen and liver.
- Composed of single or multiple masses of neoplastic endothelial cells. - What is the subtype of angiosarcoma?
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Hepatic Angiosarcoma: rare but associated with carcinogens, including arsenic, thorotrast,
or (polyvinyl chloride, PVC). - Define hemangiopericytoma
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Rare, malignant neoplasm that presumably arises from pericytes.
The tumor presents numerous branching capillary channels surrounded by and enclosed within nests and masses of spindle-shaped cells.
Metastatic rate: 10-50%