Histology and Cell Biology of blood vessels and lymphatics

Layers of walls of arteries and veins

tunica intima, tunica media, tunica externa

Nervi vasorum (vascularis)

- 'vasoconstrictor nerves' which represent unmyelinated postsynaptic sympathetic nerve fibers. -release NE as their synaptic NT resulting in vasoconstriction

small veins

-less than 1 mm in diameter -continuous with muscular venules.

atherosclerosis

-Atherosclerotic lesions are the most common acquired abnormality of blood vessels -Ischemic heart disease, MI, stroke and gangrene of the limbs can all be complications of atherosclerotic disease -Lesions are typically formed in the tunica intima of large elastic arteries following endothelial injury, leading to endothelial dysfunction -Predisposing factors: high-LDL, hyperlipidemia, hyperglycemia (DM), HTN, cigarette smoking, and certain viral and bacterial infections caused by cytomegalovirus (CMV) or Chlamydia pneumoniae, respectively. -Altered function of vascular endothelium leads to increased expression of surface adhesion molecules, increased permeability to LDL, and increased adherence of WBCs to the endothelium

Metarterioles

-metarterioles allow some blood to pass more directly from artery to vein

Tunica media

- middle layer of the vessel -Primarily circumferentially arranged layers of the vascular smooth muscle cells -Thick layer in arteries extends from the internal elastic membrane to the external elastic membrane -The external elastic membrane (thin elastin layer) separates the tunica media from the tunica adventitia -Variable amounts of elastin, reticular fibers and proteoglycans are interposed b/t the sm. muscle cells of the tunica media -All of the extracellular components of the tunica media are produced by vascular sm. muscle cells

how do arterioles control blood flow to capillary networks

-Arterioles control blood flow to capillary networks by contraction of the sm. muscle cells. -Normally contraction of the sm. muscle in the wall of an arteriole increases the vascular resistance and reduces or shuts off the blood going to the capillaries. -The slight thickening of the sm. muscle at the origin of a capillary bed from an arteriole is called the precapillary sphincter -Most arterioles can dilate 60% to 100% from their resting diameter, and can maintain up to 40% constriction for a long time. -A large decrease or increase in vascular resistance has a direct effect on distribution of blood flow and systemic arterial pressure (directing blood where it is most needed)

Arteriovenous Shunts

-Arteriovenous anastomoses or AV shunts: direct routes b/t arteries and veins that divert blood from capillaries -Commonly found in skin of fingertips, nose, and lips, and in the erectile tissue -The arteriole of AV shunts is often coiled, w/relatively thick sm. muscle layer, is enclosed in a CT capsule, and is richly innervated -contraction of the arteriole sm. muscle of the AV shunt sends blood to a capillary bed; relaxation of the sm. muscle sends blood to a venule, bypassing the capillary bed -Serve in thermoregulation at the body surface -Closing an AV shunt in the skin causes blood to flow through the capillary bed, enhancing heat loss -Opening an AV shunt directs blood flow into the corpora cavernosa, initiating the erectile response

Functional aspects of capillaries

-Blood flow is controlled through local and systemic signals -Vasodilating agents (NO, low O2 tension) cause sm. muscle relaxation in arteriole walls -Pressure w/in capillaries increases and plasma fluid is driven into tissue (peripheral edema) -Vasoconstriction (local endothelial-derived factors, systemic signals from the ANS and NE released by the adrenal gland) cause sm. muscle contraction -Decreased blood flow in the capillary bed -Capillary pressure can decrease and increase absorption of tissue fluid -Occurs during loss of blood volume -Can add considerable amt. of fluid to the blood preventing hypovolemic shock -Density of capillary network determines the total surface area available for exchange b/t the blood and tissue -Related o metabolic activity of the tissue -Liver, kidney, cardiac and sk. muscle have rich capillary networks -Dense CT is less metabolically active and has less extensive capillary networks

Capillaries

-Capillaries are the smallest diameter blood vessels, often smaller than the diameter of an erythrocyte -Capillaries form blood vascular networks that allow fluids containing gases, metabolites, and waste products to move through their thin walls -Consist of a layer of endothelial cells and their basal lamina -The endothelial cells form a tube large enough to allow passage of RBCs one at a time -The lumen of many capillaries is so narrow that RBCs must fold in order to pass through -Capillaries thin walls and close association with metabolically active cells and tissues make capillaries well suited for exchange of gasses and metabolites

precapillary sphincter

-Capillaries arise from arterioles and metarterioles 'capillaries themselves have no sm. muscle in their walls but have a sphincter of sm. muscle (precapillary sphincter) located at their origin from either an arteriole or a metarteriole

DVT

-Deep veins of lower limbs are often the site of thrombus formation (DVT) -DVT is associated with immobilization of the lower limbs -can be a life-threatening condition due to potential for development of PE

Endothelium-derived hyperpolarizing factor (EDHF)

-EDHF is an EDRF that acts on Ca2+ dependent channels causing hyperpolarization of vascular sm. muscle cells and their relaxation

Veins

-tunics of veins are not as distinct or well defined as the tunics of arteries -veins are traditionally divided based on size: venules, small veins, medium veins, large veins -Medium and large veins have three layers: tunica intima, media and adventitia though the layers are not as distinct as in arteries -Large and medium sized veins usually travel with large and medium sized arteries -Arterioles and muscular venules sometimes travel together -Veins typically have thinner walls than accompanying arteries and the lumen of veins is larger -Arteriole lumen is typically patent while vein lumen is often collapsed -Many veins contain valves that allow blood to flow in only one direction (back to the heart) -Valves are semilunar flaps consisting of thin CT core covered w/endothelial cells

Formation of atherosclerotic plaques

-Endothelial injury increases the production of ROS (O2−, H2O2, OH−, and ONOO−) which oxidize LDL in the tunica intima of the artery -monocytes from the bloodstream enter the tunica intima and differentiate into macrophages -Macrophages phagocytize oxidized LDL (transform into foam cells w/a spongy appearance) -Foam cells and infiltrated T lymphocytes form the initial atherosclerotic lesion (fatty streak) -In this early lesion, vascular sm. muscle cells from the tunica media proliferate and migrate toward the fatty streak in response to PDGF produced by endothelial cells. -later the lesion undergoes remodeling and growth into fibrofatty plaque -sm. muscle cells migrate from the media and synthesize collagen to form a protective capsule of CT that encloses the growing lipid core -A thick layer of fibrous CT containing scattered sm. muscle cells, macrophages, foam cells, T lymphocytes, cholesterol crystals, and cell debris is known as an atheromatous plaque

Endothelial-derived relaxing factor

-Endothelial-derived relaxing factor (EDRF) causes relaxation of blood vessels. -most vascular effects of EDRF can be attributed to NO and its related compounds, released by endothelial cells in arteries, blood capillaries, and even lymphatic capillaries. -NO is a gas with a very short physiologic half-life (seconds)

Continuous capillaries

-Found in CT; cardiac, skeletal and smooth muscle; skin; lungs and the CNS -Characterized by uninterrupted vascular endothelium that rests on a continuous basal lamina -Endothelial cells are individually joined by tight junctions which restrict passage of molecules b/t adjacent endothelial cells (allowing only the passage of relatively small molecules)

ischemic event

-Ischemic event: characterized by anginal pain associated with loss of oxygenated blood flow to the region of the heart supplied by the affected coronary vessel -Coronary artery thrombosis usually precedes and precipitates an MI -Mural thrombus may develop; usually associated with dysfunctional or ruptured endothelium overlying atheromatous plaque -With time, the area of the heart affected by the MI heals; a scar forms and replaces damaged tissue, but the area of infarction loses contractile function -Multiple infarctions over time can produce sufficient loss of cardiac function to cause death -Infarction also commonly occurs in the brain, spleen, kidney, lung, intestine, testes, and tumors (especially of the ovaries and uterus)

Ischemic Heart disease

-Ischemic heart disease/ischemic cardiomyopathy: the imbalance between supply and demand of the heart for oxygenated blood -most common type of heart disease in the US -most common cause of ischemic heart disease is atherosclerosis -risk of developing atherosclerosis increases with age, FH, HTN, cigarette smoking, hypercholesterolemia, and diabetes. -Atherosclerosis causes the lumina of the coronary arteries progressively narrow -Blood flow becomes critical when it is reduced by 90% or more. -Sudden occlusion of the narrowed lumen by a thrombus released from the surface of an atheromatous plaque precipitates an acute ischemic event

structure of lymphatic capillaries

-Lymphatic capillaries are essentially tubes of endothelium that, unlike the typical blood capillary, lack a continuous basal lamina. -incomplete basal lamina = high permeability -Anchoring filaments extend between the incomplete basal lamina and the perivascular collagen -Anchoring filaments consist of fibrillin microfibrils (composed of fibrillin-1 molecules and microfibril-associated protein emilin-1) -Anchoring filaments maintain the patency of the vessels during times of increased tissue pressure, such as in inflammation. -Deficiency in emilin-1 synthesis in animals is related to structural and functional defects of lymphatic capillaries.

lymphatic capillaries

-Lymphatic capillaries are more permeable than blood capillaries and collect excess protein-rich tissue fluid. -more effective than blood capillaries in removing protein-rich fluid from the intercellular spaces -specialized in the uptake of inflammatory molecules, dietary lipids, and immune cells -Lymphatic vessels convey proteins and lipids that are too large to cross the fenestrations of the absorptive capillaries in the small intestine. -lymph passes through lymph nodes before it is returned to the blood, where it is exposed to the immune system cells -Antigens conveyed in lymph are trapped by follicular dendritic cells -Antigens expressed on follicular dendritic cells can be processed by APCs in the lymph node

Lymphatic vessels

-Lymphatic vessels convey fluids from the tissues to the bloodstream. -serve as adjuncts to the blood vessels -unidirectional, conveying fluid only from tissues -The smallest lymphatic vessels are called lymphatic capillaries -Especially numerous in loose CT under epithelium of skin and mucous membranes -begin as "blind-ended" tubes in the microcapillary beds and converge into increasingly larger collecting vessels called lymphatic vessels. -They ultimately unite to form two main channels that empty into the blood vascular system by draining into the large veins in the base of the neck. -lymph enters the vascular system at the junctions of the internal jugular and subclavian veins -The largest lymphatic vessel, draining most of the body and emptying into the veins on the left side, is the thoracic duct -The other main channel is the right lymphatic trunk

synthesis of NO

-NO is an endogenous vasodilatory gas continuously synthesized in endothelial cells by endothelial nitric oxide synthase (eNOS). -eNOS is a Ca2+-dependent enzyme that catalyzes oxidation of L-arginine and acts through the G protein signaling cascade. -Endothelial cells are constantly subjected to shear stress which increases synthesis of an eNOS stimulator (VEGF) and triggers a variety of other molecular and physical changes in endothelial cell structure and function. -After NO production by endothelial cells, it diffuses out through the cell and basement membrane to the tunica media and binds to guanylate cyclase in sm. muscle cytoplasm. -guanylate cyclase increases cGMP production (activates sm. muscle protein kinase G (PKG)) -Activation of PKG causes sm. muscle relaxation

pericytes

-Pericytes represent undifferentiated mesenchymal stem cells -Pericytes and endothelial cells synthesize and share the basal lamina, synthesize growth factors, and communicate with each other through tight and gap junctions. -Pericyte coverage is more extensive in the postcapillary venules than in the capillaries.

progression of atherosclerotic plaque

-Progression of the plaque is marked by accumulation of lipids and increased activity of matrix-degrading enzymes with accumulation of necrotic tissue -Gradual loss of the vascular sm.muscle cells by apoptosis and loss of integrity of the endothelium leads to plaque rupture with subsequent thrombosis -In advanced lesions, blood stasis and clotting may lead to vessel occlusion -Progression from simple to complicated lesions can be found in some people as early as their 20s and in most individuals by age 50 or 60 years.

Pericytes (Rouget cells)

-Represent a population of undifferentiated mesenchymal stem cells that are associated with capillaries -they intimately surround the capillary with branching cytoplasmic processes and are enclosed by a basal lamina that is continuous with that of the endothelium -Pericytes are contractile and controlled by NO -Provide vascular support and promote stability of capillaries and postcapillary venules through bidirectional physical and chemical communication with vascular endothelial cells -Histologically: display features of undifferentiated mesenchymal stem cells with large nuclei rich in heterochromatin -environmental signals can stimulate proliferation, migratory capability, and differentiation of pericytes into a variety of cell types, including adipocytes, fibroblasts, chondrocytes, osteocytes, and skeletal muscle cells -Pericytes give rise to endothelial cells and sm. muscle cells during embryonic development and angiogenesis -Directly involved in pathogenesis of vascular driven diseases -Uncontrolled division of pericytes give rise to hemangiopericytoma, a rare vascular tumor that can originate anywhere there are capillaries

small arteries/arterioles

-Small arteries/arterioles are distinguished from one another by the number of sm. muscle layers in the tunica media -arterioles have only one or two layers, and small arteries may have as many as eight layers of smooth muscle in their tunica media -Small arteries and arterioles are distinguished from one another by the number of smooth muscle cell layers in the tunica media. -In small arteries the tunica intima typically has an internal elastic membrane; this layer may or may not be present in the arteriole. -The endothelium in both is essentially similar to endothelium in other arteries, except gap jxns may be found b/t endothelial cells and the smooth muscle cells of the tunica media. -the tunica adventitia is a thin, ill-defined sheath of CT that blends with the CT in which these vessels travel.

medium arteries/muscular arteries

-Some of these arteries are difficult to classify b/c they have features that are intermediate between the two types. -Muscular arteries have more sm. muscle and less elastin in the tunica media than do elastic arteries -The amt. of elastic material decreases b/t elastic arteries and large muscular arteries -w/decrease of elastic material, sm. Muscle cells become the predominant cell type of the tunica media -Internal elastic membrane becomes apparent (sometimes a recognizable external elastic membrane is also evident)

Circulation of lymphocytes in lymphatic and blood vessels

-The circulation of lymphocytes through the lymphatic vessels and the bloodstream enables them to move from one part of the lymphatic system to another at different stages in their development and to reach sites within the body where they are needed -Lymphocytes conveyed in the lymph enter lymph nodes via afferent lymphatic vessels -lymphocytes conveyed in the blood enter the node through the walls of postcapillary venules (HEVs) -B and T cells migrate to and populate different regions within the lymph node. -Some lymphocytes pass through the substance of the node and leave via the efferent lymphatic vessels (lead to the right lymphatic trunk or to the thoracic duct) -the right lymphatic trunk and thoracic duct empty into the blood circulation at the junctions of the internal jugular and subclavian veins at the base of the neck -The lymphocytes are conveyed to and from lymphatic tissues via the blood vessels.

Vascular endothelium

-The circulatory system is made up of vessels lined by a simple squamous epithelium (endothelium) -The endothelium is formed by a continuous layer of flattened, elongated and polygonally shaped endothelial cells that are aligned w/their long axes in the direction of blood flow -At the luminal surface endothelial cells express a variety of surface adhesion molecules and receptors -Endothelial cells play important roles in blood homeostasis

tunica adventitia of muscular arteries

-The tunica adventitia of muscular arteries is relatively thick and is often separated from the tunica media by a recognizable external elastic membrane. -consists of fibroblasts, collagen fibers, elastic fibers, and sometimes scattered adipose cells. -The tunica adventitia is relatively thick compared to elastic arteries -Collagen fibers are the principal extracellular component. -A concentration of elastic material immediately adjacent to the tunica media is often present constituting the external elastic membrane -Nerves and small vessels travel in the adventitia and give off branches that penetrate into the tunica media in the large muscular arteries as the vasa vasorum

Tunica intima of muscular arteries

-The tunica intima is relatively thinner in muscular arteries than in elastic arteries and consists of an endothelial lining with its basal lamina, a sparse subendothelial layer of CT, and a prominent internal elastic membrane. -The thickness of the tunica intima varies with age and other factors. -young children: very thin -young adults: the tunica intima accounts for about 1/6 of the total wall thickness of muscular arteries -older adults: the tunica intima may be expanded by lipid deposits, often as irregular "fatty streaks."

tunica media of muscular arteries

-The tunica media of muscular arteries consists of vascular sm. muscle cells along with collagen fibers and relatively little elastic material. -The sm. muscle cells are arranged in a spiral fashion in the arterial wall. -Sm. muscle cell contraction helps maintain BP -there are no fibroblasts in this layer (same as elastic arteries) -The smooth muscle cells possess a basal lamina except at the sites of gap junctions and produce extracellular collagen, elastin, and ground substance.

Fenestrated capillaries

-Typically found in endocrine glands and sites of fluid or metabolite absorption, such as the gallbladder, kidney, pancreas, and intestinal tract -Endothelial cells are characterized by the presence of fenestrations (circular openings that provide channels across the capillary walls -Continuous basal lamina is found on the basal plasma membrane surfaces -Endothelial cells in both fenestrated and continuous capillaries have numerous pinocytic vesicles - A fenestration may have a thin, non-membranous diaphragm across its opening. -fenestrations constitute specific transport sites within the endothelial cells, also referred to as filtration pores, and are not free for passage of plasma like the gaps between endothelial cells in sinusoidal capillaries -Fenestrated capillaries in the GI tract and gallbladder have fewer fenestrations and a thicker wall when no absorption is occurring. When absorption takes place, the walls thin, and the number of pinocytotic vesicles and fenestrations increases rapidly -Ionic change in perivascular CT stimulates pinocytosis

Discontinuous capillaries (sinusoidal capillaries/sinusoids)

-Typically found in the liver, spleen and bone marrow - large in diameter and more irregular in shape than other capillaries -Vascular endothelial cells in these capillaries have large openings in their cytoplasm and are separated by wide, irregular, intercellular gaps that allow for passage of blood plasma proteins -Endothelial cells rest on a discontinuous basal lamina -Structural variability b/t organs -Kupffer cells (stellate sinusoidal macrophages) and vitamin A storing Ito cells (hepatic stellate cells) in the liver are associated with endothelial cells of hepatic sinuses -In spleen endothelial cells exhibit a unique spindle shape with gaps b/t the neighboring cells (basal membrane is rudimental in these capillaries and may be partially or completely absent)

Venules

-Venules are further subclassified as postcapillary and muscular venules -receive blood from capillaries have a diameter as small as 0.1 mm -include post capillary venules, high endothelial venules (HEVs) and muscular venules

Great saphenous vein

-a long subcutaneous vein of the lower limb that originates in the foot and drains into the femoral vein just below the inguinal ligament -often described as a muscular vein because of the presence of an unusual amount of smooth muscle -Possesses a thick circular arrangement of sm. muscle in its tunica media as well as numerous longitudinal smooth muscle bundles in the intima and in the well-developed adventitia -A thin, poorly developed internal elastic membrane separates the tunica intima and media -frequently harvested from the lower limb and used for autotransplantation in CABG surgery when arterial grafts (usually taken from the internal thoracic artery) are not available or many grafts are required for multiple-bypass anastomoses

Postcapillary venules

-collect blood from the capillary network and are characterized by the presence of pericytes. -Post capillary venules possess an endothelial lining with its basal lamina and pericytes -The endothelium of postcapillary venules is the principal site of action of vasoactive agents such as histamine and serotonin -These vasoactive agents cause extravasation of fluid and migration of WBCs from the vessel during inflammation and allergic reactions -Postcapillary venules of lymph nodes participate in the transmural migration of lymphocytes from the vascular lumen into the lymphatic tissue. -Pericyte coverage is more extensive in the postcapillary venules than in the capillaries.

Coronary arteries

-considered medium sized muscular arteries -originate from the proximal part of the ascending aorta and lie on the surface of the heart in the epicardium surrounded by adipose tissue -coronary arteries walls are usually thicker than comparable arteries in the limbs b/c of large amounts of circular smooth muscle layers in the tunica media -the subendothelial layer of the tunica intima of younger people is inconspicuous but progressively thickens by increasing amounts of sm. muscle cell and fibroelastic tissue with aging -The internal elastic membrane is well developed (though maybe fragmented, duplicated, or focally lost) in older individuals. -The relatively "loose" consistency of the tunica adventitia is reinforced by the longitudinal bundles of collagen fibers allowing for continuous changes of the vascular diameter -Atherosclerotic changes in coronary arteries can lead to ischemic heart disease

Muscular venules

-distinguished from postcapillary venules by the presence of a tunica media. -located distal to the postcapillary venules -diameter of as much as 0.1 mm. -muscular venules have 1-2 layers of vascular sm. muscle that constitute a tunica media -also possess a thin tunica adventitia -Pericytes are usually not present

endothelial activation

-endothelial activation: functional properties of endothelial cells change in response to various stimuli -Endothelial activation can be induced by bacterial and viral antigens, cytotoxins, compliment products, lipid products and hypoxia -Activated endothelial cells exhibit new surface adhesion molecules and produce different classes of cytokines, lymphokines, growth factors, and vasoconstrictor and vasodilator molecules, as well as molecules that control blood coagulation.

large veins

-have a diameter greater than 10 mm -Ex. SVC and IVC and hepatic portal vein -tunica media is relatively thin, and the tunica adventitia is relatively thick -tunica intima of these veins consists of an endothelial lining with its basal lamina, a small amount of subendothelial CT, and some sm. muscle cells -the boundary between the tunica intima and media is often not clear, and it is not always clear whether -The tunica media is relatively thin and contains circumferentially arranged sm. muscle cells, collagen fibers, and some fibroblasts. -The tunica adventitia of large veins is the thickest layer of the vessel wall -The tunica adventitia contains longitudinally disposed sm. muscle as well as the usual collagen and elastic fibers -Atrial myocardial extensions known as myocardial sleeves are present in the adventitia of the SVC and IVC as well as the pulmonary trunk. -Myocardial extensions vary in different individuals -Postmortem exam of pulmonary veins from patients with afib frequently reveal presence of myocardial sleeves w/altered cardiac muscle cells.

Large arteries/elastic arteries

-include arteries such as the aorta and pulmonary arteries which convey blood from the heart to systemic and pulmonary circulatins -elastic arteries have multiple sheets of elastic lamella in their walls -elastic arteries serve primarily as conduction tubes but also facilitate the continuous and uniform movement of blood along the tube

Endothelial cell properties and functions

-maintenance of a selective permeability barrier -maintenance of non-thrombogenic barrier (secretion of anticoagulants, antithrombogenic agents and prothrombogenic agents) -modulation of blood flow and vascular resistance (secretion of vasoconstrictors and vasodilators) -regulation of cell growth (secretion of growth stimulating and growth inhibiting factors) -regulation of immune response (regulation of leukocytes migration through expression of adhesion molecules and immune fxns) -maintenance of ECM (synthesis of basla lamina and glycocalyx) -involvement in lipoprotein, cholesterol, metabolism (production of free radicals, oxidation of LDL)

medium veins

-most of the named veins -usually are accompanied by arteries -have a diameter of as much as 10 mm -Most deep veins that accompany arteries are in this category -Valves are a characteristic of these vessels (most numerous in the inferior portion of the body (particularly lower limbs) to prevent retrograde movement of blood because of gravity) -The three tunics of the venous wall are most evident in medium veins -tunica intima: consists of endothelium with its basal lamina, a thin subendothelial layer with occasional sm. muscle cells scattered in the CT elements, and sometimes a thin often discontinuous internal elastic membrane. -tunica media: is much thinner in medium veins than the same layer in medium arteries -contains several layers of circularly arranged sm. muscle cells w/interspersed collagen and elastic fibers -longitudinally arranged sm. muscle cells may be present just beneath the tunica adventitia -tunica adventitia: is typically thicker than the tunica media and consists of collagen fibers and networks of elastic fibers

Central adrenomedullary vein

-passes through the adrenal medulla and its tributaries -has an unusual tunica media -contains several longitudinally oriented bundles of sm. muscle cells that vary in size and appearance -These irregularly arranged sm. muscle bundles (muscle cushions) extend into larger tributaries of the central adrenomedullary vein -The arrangement of sm. muscle bundles results in irregularity in the thickness of the vascular wall -In areas where muscle bundles are absent, cells of the adrenal medulla or sometimes adrenal cortex are separated from the lumen of the vein only by a thin layer of the tunica intima -Contraction of the longitudinally arranged sm. muscles in the tunica media enhances the efflux of hormones from the adrenal medulla into the circulation

Weibel palade bodies

-present in endothelial cell cytoplasm -electron dense structures that contain von Willebrand factor and P-selectin

Endothelins

-produced by vascular endothelial cells and play important roles in physiologic and pathologic mechanisms of the circulatory system -cause vasoconstriction in the tunica media of small arteries and arterioles -vasoconstriction increases systemic BP -members of the endothelin family produced by vascular endothelial cells are the most potent vasoconstrictors -endothelin-1, -2, and -3 (ET-1, -2, and -3): mainly act as paracrine and autocrine agents and bind to epithelial cells and vascular sm. muscles

tunica adventitia of elastic arteries

-relatively thin CT layer -usually less than half the thickness of the tunica media -consists of collagen and elastic fibers forming a loose network of elastic fibers (not lamellae) that are less organized than those of the tunica media -collagen fibers prevent expansion of the arterial wall beyond physiologic limits during systole -fibroblasts and macrophages are the principal cells of the tunica adventitia -vasa vasorum can be found in this layer -nervi vasorum is also located in this layer

prostacyclin (PGI2)

-relaxes sm. muscle and is a potent inhibitor of platelet aggregation -PGI2 binds to receptors on the sm. muscles; stimulates cAMP-activated PKA, which phosphorylates myosin light chain kinase; and prevents activation of the ca-calmodulin complex -this relaxation occurs w/o change in the intracellular Ca2+ concentration

Dural venous sinuses

-represent venous channels in the cranial cavity -essentially broad spaces within the dura mater that are lined with endothelial cells and devoid of sm. muscles

The effect of shear stress on vascular endothelial cells

-shear stress during interaction of blood flow w/vascular endothelial cells initiates NO-derived relaxation of blood vessels (vasodilation) -endothelium derived NO is one of several critical regulators of cardiovascular homeostasis -NO regulates blood vessel diameter, inhibits monocyte adhesion to dysfunctional endothelial cells, and maintains an antiproliferative and antiapoptotic environment in the vessel wall. -NO is an endogenous vasodilatory gas continuously synthesized in endothelial cells by endothelial nitric oxide synthase (eNOS). -NO is also a signaling molecule in many pathological and physiological processes

Vasa vasorum (blood vessels)

-small arterial branches, their capillary network, and corresponding veins -Deliver nutrients and O2 to the vascular wall and remove waste products -consists of small arteries entering the vascular wall from outside the vessel and dividing into a network of arterioles and capillaries supplying the outer part of the wall. Small veins emerging from the vasa vasorum drain the capillaries and venules into larger veins that accompany the arteries. -inner part of the vascular wall is supplied by diffusion of nutrients from the lumen. -vessels with a lumen < 0.5 mm diameter usually do not have a vasa vasorum (tunica media is usually thinner than a 30-cell layer) -There is a strong association between the higher density of vasa vasorum in an arterial wall and the severity of atheromatous plaque formation.

High endothelial venules (HEVs)

-specialized postcapillary venules found in lymphoid tissues -support high levels of lymphocyte migration from the blood -HEVs have a prominent cuboidal appearance of their endothelial cells and ovoid nuclei. -found in all secondary (peripheral) lymphatic organs (with the exception of the spleen) -lymph nodes, tonsils, and lymph nodules -HEV endothelium can recruit large amount of lymphocytes -contain prominent Golgi, abundant polyribosomes and an extensive rER -Typical features for secretory fxn -Also contain secretory vesicles, multivesicular bodies, transport vesicles and Weibel-Palade bodies

HTN

-sustained DBP greater than 90mmHg or sustained SBP greater than 140 -HTN is associated with atherosclerotic vascular disease and increased risk of CV disorders -in most cases of HTN the luminal diameter of sm. muscular arteries and arterioles is reduced (increased vascular resistance) -sm. muscle cells multiply in pts. w/HTN -additional sm. muscle adds to the tunica media and some of the sm. muscle cells accumulate lipid -HTN increases the rate of intimal thickening that occurs w/age -cardiac muscle is also affected by HTN leading to pressure overload and compensatory LV hypertrophy -ventricular hypertrophy w/HTN is caused by increased diameter of cardiac muscle cells w/o characteristic enlarged and rectangular nuclei -untreated HTN will lead to cardiac failure

Tunica intima

-the innermost layer of the vessel -Consists of three components: 1. Single layer of squamous epithelial cells (endothelium) -Contains sheet-like layer/lamella of fenestrated elastic material (internal elastic membrane) -Fenestration allow for diffusion of substances through the layer to reach cells deep w/in the vessel wall 2. Basal lamina of the endothelial cells: thin extracellular layer of collagen, proteoglycans and glycoproteins 3. Subendothelial layer: loose CT

structure of lymphatic vessels

-the lymphatic vessels exhibit features to prevent lymph from leaking out of their lumens. -possess continuous tight junctions between the endothelial cells and continuous basal lamina surrounded by sm. muscle cells -As lymphatic vessels become larger, the wall becomes thicker. -Increased thickness is due to CT and bundles of sm. muscle. -Lymphatic vessels possess valves that prevent backflow of the lymph -There is no central pump in the lymphatic system -Lymph moves sluggishly, driven primarily by compression of the lymphatic vessels by adjacent sk. muscles -contraction of the smooth muscle layer surrounding lymphatic vessels may help propel the lymph.

Endothelin-1 (ET-1)

-the most potent naturally occurring vasoconstricting agent that interacts with its ETA receptor on vascular sm. muscles -High levels of ET-1 gene expression are associated w/many diseases caused in part by sustained endothelium-induced vasoconstriction (systemic HTN, pHTN, atherosclerosis, CHF, idiopathic cardiomyopathy and renal failure)

Tunica adventitia

-the outermost CT layer of vessels -Composed of longitudinally arranged collagenous tissue and a few elastic fibers -The CT elements gradually merge with loose CT surrounding the vessels -Relatively thin in most of the arterial system -Relatively thick in venules and veins (where it is the major component of the vessel wall) -The tunica adventitia of large arteries and veins contains a system of vessels called the vasa vasorum that supplies blood to the vascular walls -Nervi vasorum (vascularis): network of autonomic nerves that control contraction of the sm. muscle in the vessel walls

Tunica intima of elastic arteries

-the tunica intima of elastic arteries is thick and consists of an endothelial lining with its basal lamina, a subendothelial layer and internal elastic membrane -the subendothelial layer consists of CT and collagen and elastic fibers -sm. muscle cells are the main cell type in the subendothelial layer (sm. muscle cells are contractile cells that secrete extracellular ground substance along w/collagen and elastic fibers) -the internal elastic membrane is one of many elastic layers in the wall of the vessel (innermost elastic layer of the arterial wall)

tunica media of elastic arteries

-tunica media of elastic arteries consists of multiple layers of VSMCs separated by elastic lamellae -thickest layer of elastic arteries -contains elastin in the form of concentric fenestrated sheets or lamellae b/t muscle cell layers -the number and thickness of lamellae are related to age and BP (basically no lamellae at birth, 40-70 layers int eh adult aorta, increased thickness with HTN) -tunica intima also contains VSMCs arranged in layers (arranged in a low-pitch spiral relative to the long axis of the vessel) -fibroblasts are not present in the tunica media -VSMCs synthesize collagen, elastin, and other ECM molecules -in response to growth factors sm. muscle cells may proliferate and migrate to the adjacent intima

Blood flow

The ventricles of the heart pump blood into the elastic arteries during systole > The pressure generated by ventricular contraction moves blood through the elastic arteries and along the arterial tree (Simultaneously, it also causes the wall of the large elastic arteries to distend (which is limited by the network of collagenous fibers in the tunica media and tunica adventitia)) > During diastole the recoil of the distended elastic arteries serves to maintain arterial BP and the flow of blood within the vessels (Initial elastic recoil forces blood both away from and back toward the heart) >The flow of blood toward the heart causes the aortic and pulmonary valves to close >Continued elastic recoil then maintains continuous flow of blood away from the heart.

Von Willebrand factor

binds to factor VIII and plays an important role in platelet adhesion during endothelial injury

P selectin

cell adhesion molecule that initiates neutrophil migration