●●● OVERVIEW OF THECARDIOVASCULAR SYSTEMThe cardiovascular system includes the blood and lymphaticvascular systems. Blood consists of cells, proteins, dissolvedgasses, nutrients, hormones, metabolic waste products, andfluids. Lymph consists of the cells of the lymphoid system and fluids.

The primary function of the cardiovascular system is todistribute blood to the entire body and to collect lymph fromperipheral organs and tissues.The blood vascular componentconsists of a pump, the heart, and an extensive system oftubes, the blood vessels, that make up a closed, circularsystem. The vessels that leave the heart are called arteries,

and those that return blood to the heart are called veins.Pumping of the heart generates an arterial blood pressure ofabout 100 mm Hg while venous blood returns to the heart ata pressure of about 5 to 10 mm Hg.

As the arteries reach their target organs (brain, kidneys,intestines, etc) or other end points (areas of loose connectivetissue, mesenteries, pia mater, etc) their diameter becomessmaller and smaller and their wall thickness thinner andthinner until the tube is composed of single cells that form acylinder, the capillaries. A schematic diagram of the cardio-vascular system is seen in Figure 7-1. This diagram illustratesthe closed circular nature of the blood vascular system and its tributaries and the unidirectional flow of lymph in thelymphatic vascular system.

The heart and blood vessels have three layers. In the heartthe layers are called endocardium, myocardium, and epi-cardium. The analogous layers in blood vessels are tunicaintima, tunica media, and tunica adventitia.

In a normal, healthy individual, many components of theblood, e.g., nutrients (glucose, amino acids, O2), vitamins,hormones, and proteins, exchange with tissue fluids and gases(with the exception of the red blood cell [RBC]).There is onesignificant exception regarding RBCs in the spleen (seeChapter 8). A certain amount of tissue fluid and white cellsare taken up by blind-end capillaries of the lymphaticcirculation, carried through an extensive branching system ofthin-walled vessels, the lymphatic vessels, and returned to theblood vascular circulation via the larger veins near the heart.

The exchange of fluid-containing nutrients and oxygenwith tissue fluids containing metabolic waste products andCO2 occurs in capillary beds, which are often referred to asmicrovascular beds or as the microcirculation. Normally, manywhite cells leave the bloodstream in the microcirculation.Most of the fluid is taken up in the distal or venous end of amicrovascular bed by a subset of vessels called postcapillaryvenules. Remaining fluid and those white cells of the immunesystem that have been immunologically stimulated or areengaged in immune surveillance are taken up by lymphaticcapillaries and thereby travel to the lymphoid organs.

Cardiovascular System,Blood, and Blood CellFormation

7

CONTENTSOVERVIEW OF THE CARDIOVASCULAR SYSTEM

GENERAL STRUCTURE OF THE HEARTHeart Valves

HEART AS A PUMPContractile Properties of Cardiac Myocytes Contraction of the HeartSystemic Regulation of Heart Rate

BLOOD VESSELSGeneral Structure of Blood VesselsCapillary StructureSpecial Characteristics of Blood VesselsSpecial Vascular Arrangements

LYMPHATIC VESSELSLymphatic CapillariesCollecting and Main Lymphatic Vessels

BLOOD AND BLOOD FORMATIONBloodBlood CellsBlood Cell FormationDevelopment of Specific Cells

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●●● GENERAL STRUCTURE OF THEHEART

The heart has four chambers: the right atrium and rightventricle and the left atrium and left ventricle. The chambersare arranged to support a two pump–two circuit circulatorysystem—the pulmonary circulation and the systemic circu-lation. The right atrium receives blood from the peripheralsystemic circulation and delivers it to the right ventricle,which pumps it to the lungs for reoxygenation. Blood isreturned to the left atrium from the lungs and then to the leftventricle. The reoxygenated blood is distributed to the bodyby contraction of the muscular left ventricle. The atria arerelatively thin-walled chambers of about equal size and wallthickness.The left ventricle is a thick walled conical chamber;the right ventricle has a thinner wall and can be thought of asa large cone-shaped covering of the outer surface of the leftventricle.The right ventricle has a larger capacity than the leftventricle, but the wall of the left ventricle is two to threetimes thicker than the right ventricle (Fig. 7-2). Heart muscleitself is nourished by an extensive network of coronaryarteries.

The majority of the mass of the heart is cardiac muscle (seeChapter 4). Compared with skeletal muscle, cardiac myocytesare surrounded by more endomysium-like connective tissue.In further contrast to skeletal muscle, cardiac muscle fibersare not organized into parallel fascicles or long bundles ofmuscle fibers. The long-range organization of cardiac musclefibers reflects two underlying characteristics: bundles of

CARDIOVASCULAR SYSTEM, BLOOD, AND BLOOD CELL FORMATION198

Adventitia

Media

Intima

Adventitia

Media

Intima

Largevein

Mediumvein

Elasticartery

Lymph node

Lymphatics

Muscularartery

Small artery

Pericyte

Venule

Capillary

Heart

Arterialsystem

Venoussystem

Figure 7-1. Diagram of thecardiovascular and lymphatic circulatorysystems. The arterial side is shown inred-colored vessels, the venous side inblue-colored vessels, and some lymphnodes and the lymphatic circulation inpurple-colored vessels. Note that thelymphatic circulation drains into theinferior vena cava through the thoracicduct, the largest diameter lymphaticvessel; this is the major site for lymph tore-enter the blood circulation althoughthere are others. A schematicrepresentation of the wall structure oftypical arteries and veins are shown neartheir location in the diagram. The threelayers of the vessel walls are colored tocorrespond to their basic tissue type.

Bundle of His

Rightventricle

Purkinje fibers

Leftventricle

Left atrium

Chordaetendinae

Pulmonaryartery

Aortic arch

Atrioventricularnode

Vena cava

Sinoatrialnode

Rightatrium

Figure 7-2. Diagram of the heart shows both atria andventricles, the ascending and descending vena cava, theaortic arch and its three branches that carry blood to thehead, and the conducting system of the heart (shown inyellow)—the sinoatrial node, atrioventricular node, the bundleof His, and the Purkinje fibers. The direction of conduction isshown by the dark blue arrows. The supporting structures ofthe valves, the chordae tendinae, are also shown.

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different sizes are organized into many oblique groups thatappear as long, intertwined spiral bundles, and when theventricles contract, they do so with a wringing-like motionwhich forcefully ejects blood into the pulmonary artery andthe aorta.

Heart Valves

The openings of the atria into the ventricles are guarded byvalves that prevent backflow. The valve between the rightatrium and ventricle is called the tricuspid valve and the onebetween the left atrium and ventricle is called the bicuspid(or mitral) valve. A large artery leaves each of theventricles—the pulmonary artery from the right ventricle andthe aorta from the left ventricle, each having a set of valvescalled the semilunar valves.These four-valved openings of theheart are in about the same anatomic plane and aresupported by dense fibrous connective tissue rings.The valvesare made of thin, tough connective tissue and are coveredwith endocardium. The innermost part of the valves iscontinuous with the fibrous rings. The atrioventricular valveshave connective tissue extensions, the chordae tendinae,which connect to muscular extensions of the inner heart wallcalled papillary muscles. The fibrous rings are called thecardiac skeleton and in some species have a cartilage-likeappearance (Fig. 7-3A). Figure 7-3B is a diagram of theatrioventricular valves and cardiac skeleton.

●●● HEART AS A PUMP

Contractile Properties of Cardiac Myocytes

Individual cardiac myocytes can be isolated from a heart andgrown in tissue culture.They retain the cylindrical shape theyhave in situ, including the step-like ends where they hadintercalated disks. If the culture medium has the correct Ca++

concentration and nutrient supply, the individual cells beat ina synchronized rhythmic manner.Thus, the cells are shown tohave intrinsic contractile properties.

Contraction of the Heart

Because of its intrinsic contractility, the heart beats in theabsence of external stimuli. Furthermore, specializedstructures (nodes and fibers) within the walls of the heartregulate the contraction rate. The specialized structures aremodifications of cardiac muscle. The nodes are called thesinoatrial (S-A) node and the atrioventricular (A-V) node.TheS-A node is also called the pacemaker node. The A-V nodecontinues into the A-V bundle (of His), which bifurcates intoright and left bundle branches, which are further subdividedinto specialized conducting cells called Purkinje fibers. Awave of contraction is initiated by the S-A node, which forcesblood from the atria into the ventricles.A subsequent wave ofcontraction begins at the apex of the heart causing theventricles to forcibly expel blood into the pulmonary arteryand the aorta.

Systemic Regulation of Heart Rate

The heart is subject to exquisite regulation of its pumping(beating) rate by the autonomic nervous system (ANS). Bothdivisions of the ANS innervate the heart. Parasympatheticfibers delivered by the vagus nerve (cranial nerve X)terminate mainly in the S-A and A-V nodes but also innervatethe myocardium. Sympathetic fibers also innervate bothnodes, the myocardium, and the coronary arteries that supplythe heart with blood. The sympathetic component causes anincrease in heart rate, and the parasymphatics cause the rateto diminish.

Specialized receptors are found in the carotid sinus and theaortic arch. One set of receptors are baroreceptors and theother are chemoreceptors. The former sense and respond tofluctuations in blood pressure, and the latter respond tooxygen, carbon dioxide, and pH changes.

●●● BLOOD VESSELS

General Structure of Blood Vessels

All blood vessels larger than capillaries have three layers:tunica intima, tunica media, and tunica adventitia. Each of

BLOOD VESSELS 199

PATHOLOGY

Hypertrophic Cardiomyopathy

The most common cause of sudden cardiac death in childrenand adolescents is hypertrophic cardiomyopathy. It is also themost common cause of sudden cardiac death in youngerathletes, accounting for about one-third of sudden deaths inthese individuals. About 10% of these cardiomyopathies arecongenital.

The congenital forms are the most common monogeniccardiac disorders and are transmitted as autosomal dominantdisorders. Hundreds of point mutations have been describedin more than 10 structural proteins of the sarcomere. Two ofthe more common mutations that lead to hypertrophiccardiomyopathy are in the β-myosin heavy chain and in thetroponin I subunit of troponin. Other mutations have beendescribed in the cardiac muscle isoforms of actin, α-tropomyosin and titin. The mechanism of the hypertrophy isthought to be an increase in the contractile force of thesarcomere, which leads to hypertrophy of the myocytes. At themicroscopic level, the normal organization of cardiac myocytebundles is highly disrupted owing to enlarged, disorganizedmyocytes and infiltrations of leukocytes. These hypertrophicchanges probably lead to sudden death as a result ofelectrically unstable myocardial function and ventriculartachyarrhythmias. The pathologic presentation is marked leftventricular hypertrophy often with a massively thickenedventricular septum, atrial enlargement, and a small leftventricular cavity. Interestingly, there is another group ofmutations in structural proteins of the sarcomere that leads toa different form of cardiomyopathy—dilated cardiomyopathy.

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the layers is characterized or dominated by a single cell type,and each layer has a characteristic matrix (Table 7-1). It isimportant to remember that the entire cardiovascular systemis lined by a single cell type, the endothelial cell. Thisspecialized simple squamous epithelial cell lines theendocardium of the heart, lines all the arteries and veins, and

makes up all the capillaries. Like the heart, larger bloodvessels receive a blood supply from outside their structurethrough a system of small vessels called the vasa vasorum.

Several features of blood vessels are helpful when one isidentifying them in sectioned material. It is common to seepaired (or companion) vessels in sections of organs or in

CARDIOVASCULAR SYSTEM, BLOOD, AND BLOOD CELL FORMATION200

Coronaryvessel

Leftatrium

Sectionthroughthe trigonumfibrosum

Leftventricle

Pulmonaryvalve

Apex

Openings tocoronary arteries

Aorticvalve

Left A-V (bicuspid ormitral) valve

Right A-V (tricuspid) valve

A

B

Mitral valve

Coronarysinus

Aorta

Figure 7-3. A, Section of the leftventricle and left atrium of a monkeyheart near the mitral valve (Milligan'strichrome stain, 17.5×). One flap of themitral valve and the beginning part of theaortic arch are seen. A section throughthe left ring of the trigona fibrosa is seenin the lower central part of the field. Thecharacteristics of the connective tissue inthis specimen are suggestive of cartilage.B, Diagram shows the trigona fibrosa,both atrioventricular valves, the aorta andpulmonary trunk. The approximatesection plane of this diagram is indicatedin the heart diagram on the left.

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neurovascular bundles that are readily dissected in a cadaver.The paired vessels are an artery and vein that are approx-imately equidistant from the heart and the capillary bed eachvessel serves. The artery in such sections is usually morecircular than the vein and has a thicker wall and smallercaliber than its companion vein. In other words, the ratio ofthe caliber of an artery to its wall thickness is always smallerthan the same ratio for its companion vein.

Blood Vessel ClassificationThe structure of the walls of blood vessels and their innerdiameters (caliber) varies in a more or less continuousmanner from the largest artery (the aorta), which has adiameter of about 25 mm, down to capillaries, which havediameters of about 5 μm, and back to the vena cava, whosediameter is about 30 mm. Blood vessels are classified byreference to their wall structure and thickness and to a lesserextent, their caliber. Furthermore, the classification is basedon the arterial side of the circulatory system; for each arterialcategory, there is a comparable venous category whosestructural characteristics and appearance are more variablethan its arterial “partner.” The following are the majorcategories of blood vessels.

Elastic ArteriesThe tunica intima of these vessels usually has a thin, suben-dothelial layer of loose connective tissue with a few fibro-blasts and a rare smooth muscle cell. They have a relativelythick tunica media with spirally arranged smooth musclecells, thick collagen fibers, and many elastin fibers.The elastinfibers are arranged into concentric fenestrated lamellae. It ishard to be precise about the thickness of the tunica adventitia,since it blends into the surrounding connective tissue; it hasnumerous blood vessels that supply the tunica media (thevasa vasorum) and some nerves.The caliber of elastic arteriesranges from about 10 mm to 25 mm. Figure 7-4 shows foursections of elastic arteries stained with three different stains

to highlight the cellular composition and the matrix contentof the tunica media of elastic arteries.

Large Muscular ArteriesThe tunica intima is a single layer of endothelial cells with ascant or absent subendothelial layer of connective tissue.Theboundary of the tunica intima and media is demarcated by aprominent layer of elastic fibers called the inner elasticlamina (IEL).The tunica media has circularly oriented smoothmuscle cells and collagen and elastin fibers. At the boundaryof the tunica media and adventitia, another prominent layerof elastin fibers is seen—the external elastic lamella (EEL).Athin tunica adventitia is present. The caliber of the largemuscular arteries ranges from about 2 mm to 10 mm.Sections of muscular arteries and companion veins are seenin Figure 7-5.

BLOOD VESSELS 201

TABLE 7-1. Cellular and Matrix Composition of Blood Vessels

Tunica Predominant Cell Type Matrix Characteristics Other Features

Intima Endothelial cells and associated — Small amounts of subendothelial basal lamina loose connective tissue containing The endothelial cells have fibroblasts and a few smooth occluding junctions between them muscle cells are found in largest

vessels

Media Smooth muscle cells and associated Collagen types I and III, many Larger vessels contain smallest lamina externa elastin fibers, proteoglycans termini of vasa vasorum

NB: the matrix components In larger vessels, occasional gap are synthesized by smooth junctions may be seen between muscle cells smooth muscle cells of the tunica

media and endothelial cells of thetunica intima

Adventitia Fibroblasts Loose connective tissue Vasa vasorum, occasional nerves

PATHOLOGY

Aneurysms and Elastic Arteries

A rather common abnormality of elastic arteries is ananeurysm, a weakening of the tunica media leading todilatation of the vessel wall. Aneurysms are found in about10% of autopsies. Most aneurysms are fusiform, and some aresaccular (balloon-like). Many are dissecting aneurysms inwhich there is a longitudinal splitting of the tunica media by ahematoma, or hemorrhage, into the muscular layer of thevessel wall. The underlying cause is a weakening of the tunicamedia. The weakening may be due to a focal bacterialinfection or a congenital factor. Laboratory studies have shownthat the amount of elastin in the dilated part of the vessel issignificantly less than in the uninvolved part and that theamount of elastin mRNA is also reduced. The incidence ofaneurysms increases with age, hypertension, and thepresence of an atherosclerotic plaque.

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A B

Vasavasorum

Collagenfibers

Elastinfibers

C D

Figure 7-4. Three elastic arteries are visible in these sections; in all cases, the tunica intima is to the right and the tunicaadventitia is to the left. None of the endothelial cells of the tunica intima are visible. A, H&E stain of the carotid artery (140×). Thesmooth muscle cells, and their nuclei, of the tunica media are readily identifiable. The fenestrated elastic lamellae of the tunicamedia are the dark red–stained, wavy fibers throughout the tunica media. This vessel has a more prominent inner elastic lamellathan the aorta, which is indicative of its transition to the morphology typical of a large muscular artery. Some coarse collagenfibers of the tunica adventitia, including a cross-section of a vasa vasorum, are visible on the left margin of the specimen. B, Orcein stain of the aorta (160×). The extensive elastic lamellae of the tunica media are well demonstrated. Essentially nocellular features are discernable with this stain, although some of the tunica adventitia, with several vasa vasorum, isrecognizable. The collagen fibers are stained a much lighter brown than the elastin fibers. C and D, Sections of monkey aortastained with Milligan’s trichrome stain (C, 80×; D, 280×). The cellular and matrix components are well differentiated with thisstain. The tunica adventitia, with many vasa vasorum, at left in part C is stained light aqua blue. Part D shows the area in the boxin part C at higher magnification; the elastin fibers are stained bright red-orange, the collagen is aqua blue, and the smoothmuscle cells are reddish magenta. A small arteriole and venule are seen at lower left, illustrating the intimate intermingling of thecells and matrix components of the tunica media.

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BLOOD VESSELS 203

A

B

Vein

Artery

Tunica intima

Tunica media

Tunica adventitia

Nerve

Vein

Artery

Tunica intima

Tunica media

Tunica adventitia

Nerve

Figure 7-5. A and B, The same neurovascular bundle (part A, H&E, 31×; part B, orcein, 31×). C, Resorcin-fuchsin elastic stain ofthe femoral artery and vein of a small mammal (80×). In part A, the thick muscular walls of the artery and the vein are evident;the arterial wall is thicker, rounder, and of smaller caliber than the vein. The nerve fiber is also well stained. In part B, the amountand distribution of elastin fibers in the artery are well demonstrated; a prominent IEL and EEL are seen. In contrast, thecompanion vein has a significant elastin content, but the elastin fibers are seen throughout the tunica media and the tunicaadventitia with no particular distribution. The nerve is noticeable because of its round, unstained shape. The paired vessels inboth sections illustrate the relationship of wall thickness, caliber, shape, and elastin content and the distribution of companionarteries and veins. The three layers of the arteries in both sections are readily identifiable. The companion muscular artery andvein in part C are larger than those in parts A and B, so the elastin fiber content is more pronounced. The structuralcharacteristics of paired vessels are well demonstrated in this specimen. Several nerve bundles are seen above the vessels. Abundle of skeletal muscle fibers is also seen at bottom right. Continued

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C

Vein

Nerves

Artery

Skeletalmuscle

Figure 7-5 cont’d.

BIOCHEMISTRY

Atherosclerosis and Muscular Arteries

Many elastic, large- and medium-sized muscular arteries maybecome occluded by intimal deposits of lipids, accumulationsof smooth muscle cells and macrophages, matrix proteins, andcalcifications. The disease that results from this process iscalled atherosclerosis. The major complications ofatherosclerosis are ischemic heart disease, myocardialinfarction, stroke, and peripheral vascular disease, which canlead to gangrene of the extremities.

The pathogenesis of atherosclerosis is complex, and manyfactors contribute to its progression. A major factor is a highblood serum level of cholesterol, a lipid component of the dietas well as a molecule synthesized by all cells of the body, inparticular by the hepatocytes, the parenchymal cells of theliver. Dietary cholesterol is metabolized by the exogenous

pathway, and cholesterol synthesized by the liver and othercells is metabolized by the endogenous pathway. In bothcases, cholesterol travels in the blood in lipoprotein particles—lipid droplets surrounded by several protein (apolipoprotein)molecules.

Four major classes of lipoprotein particles are described:■ Chylomicrons are particles containing cholesterol and

triglycerides, which are assembled in the intestinal epithelialcells and delivered to lymphatic capillaries in the laminapropria of intestinal villi.

■ Very low density lipoproteins (VLDLs), particles that areproduced in hepatocytes and secreted directly into thebloodstream.

■ Low-density lipoproteins (LDLs), the major form ofatherogenic lipoproteins, which are taken up predominantlyby the liver

■ High-density lipoproteins (HDL).The triglycerides in chylomicrons are removed in capillaries

and by the cells in adipose and muscle tissue. This leaves asmaller version of lipoprotein particle rich in cholesterol andprotein called intermediate-density lipoprotein (IDL) and LDL.

IDL and LDL particles are taken up by hepatocytes andother cells wherein the cholesterol is metabolized for excretionor for other cellular use (e.g., cellular membranes, hormones).

Impaired ability to remove the lipoprotein particles from thecirculation leads to increased serum cholesterol levels and ahigher incidence of atherosclerosis.

Of at least four monogenic diseases that affect cholesteroluptake, the best characterized is familial hypercholesterolemia,which causes a deficit in the number of LDL receptors (LDLRs)per cell. It is an autosomal dominant disease, the gene forwhich is located on the short arm of chromosome 19. Morethan 600 mutations have been identified in the LDLR gene.One in 500 people is heterozygous for one such mutation, butonly one in one million is homozygous for a mutation at asingle locus. Individuals who are heterozygous produce halfthe normal number of LDLR proteins and have serumcholesterol levels two to three times normal. Homozygousindividuals have extremely low levels of LDLR proteins andserum cholesterol levels six to ten times normal. The diseaseaffects children in the first decade of life.

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Essentially all named arteries (and veins) are in the elasticand muscular categories.

Small Muscular ArteriesThe tunica intima is a single layer of endothelial cells. Thetunica media has a prominent IEL but no EEL, circularlyarranged smooth muscle cells, and more collagen fibers thanelastin fibers. A thin tunica adventitia is present. The caliberof the small muscular arteries ranges from about 0.1 mm to 2 mm. Two specimens of small muscular arteries andcompanion veins are seen in Figure 7-6.

Arterioles and MetarteriolesThe tunica intima is a single layer of endothelial cells. Thetunica media has a few layers of circularly arranged smoothmuscle cells and some collagen fibers. A thin tunica adven-titia is present. These vessels are found at the beginning ofmicrovascular beds. The smooth muscle cells have receptorsfor epinephrine and norepinepherine (potent vasocon-strictors), which contract, thereby occluding the vessel andclosing down the microvascular bed.Thus, they are importantregulators of the microcirculation. Their caliber ranges fromabout 10 μm to 100 μm.A whole mount preparation of smallvessels from the pia mater is seen in Figure 7-7.

CapillariesThe wall of a capillary consists of a single cell endotheliallayer and its basal lamina. Occasionally a special cell calledthe pericyte is seen (see Pericytes). Important variations ofcapillary structure are also discussed below. Their caliberranges from about 5 μm to 10 μm. Two small capillary bedsare seen in Figure 7-8.

Postcapillary VenulesThese vessels have a simple wall made of a single endothelialcell layer, its basal lamina, an occasional smooth muscle cell, and pericytes. They are the primary site for the trans-mural migration of lymphocytes from the circulation to theinterstitial space and back. Their caliber ranges from about10 μm to 50 μm.

VenulesThe tunica intima is a single layer of endothelial cells. Thetunica media has one to two layers of circularly arrangedsmooth muscle cells. The tunica adventitia is thicker than the tunica media. Their caliber ranges from about 50 μm to100 μm. Several venules and postcapillary venules are seen inFigure 7-8.

Small VeinsThe tunica intima is a single layer of endothelial cells with oneto two layers of smooth muscle cells.The tunica media has twoto four layers of circularly arranged smooth muscle cells(continuous with the smooth muscle cells of the tunica intima)and collagen fibers. The tunica adventitia is thicker than thetunica media. Their caliber ranges from about 0.1 mm to 2 mm.A good example of a small vein is seen in Figure 7-9.

Medium VeinsThe tunica intima is a single layer of endothelial cells andsome smooth muscle cells.These veins have valves made of athin elastic connective tissue flap covered on both surfaces byendothelial cells. The tunica media has four to ten layers ofcircularly arranged smooth muscle cells, collagen fibers, andelastin fibers. The larger veins in this category may have anincomplete IEL. The tunica adventitia is thicker than thetunica media. The larger veins in this category have isolatedbundles of longitudinally oriented smooth muscle cells.Theircaliber ranges from about 2 mm to 10 mm.Veins of this typeare seen in Figure 7-5.

Large (Elastic) VeinsThe tunica intima is a single layer of endothelial cells andsubendothelial connective tissue. Large veins may also havevalves. The tunica media has ten or more layers of circularlyarranged smooth muscle cells, many collagen fibers, andelastin fibers.The elastin fibers are not organized into distinctlamellae.The tunica adventitia is much thicker than the tunicamedia and has numerous isolated bundles of longitudinallyoriented smooth muscle cells.Their caliber ranges from about10 mm to 30 mm. Some examples of the vena cava are seenin Figure 7-10.

Capillary Structure

Capillaries are the smallest and most numerous of the bloodvessels; estimates tell us there are thousands of miles of themin our bodies.Their average diameter is about that of an RBC,7 to 8 μm, but some are only about 5 μm in diameter, so inthe smallest of capillaries RBCs become distorted, squeezingtheir way through the lumen. Yet their total cross-sectionalarea is about 600 times that of the aorta. The implications of this geometry impart significant advantages to capillaryfunction because● The flow rate of blood through a capillary is very slow.● Capillary hydrostatic pressure is nearly zero.● The diffusion path for the exchange of gases, nutrients,

fluids, and waste products is minimized.● The ratios of capillary volume to endothelial surface area

and to thickness favor efficient bidirectional exchange ofmaterials between the capillary and the extracellularspace.

From a structural point of view, there are three types ofcapillaries:● Continuous capillaries are found in all types of muscle,

the central nervous system, the lung, exocrine glands,connective tissue layers of the skin, etc.

● Fenestrated capillaries are found in the intestines,gallbladder, endocrine glands, and kidney. There are twokinds of fenestrated capillaries—those with closedfenestrations (the most common) and those with openfenestrations, which are found only in the glomerularcapillaries of the renal corpuscle.

● Discontinuous capillaries are found only in the liver.Capillaries are difficult to see in sections in the light micro-

BLOOD VESSELS 205

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A

B

Companion vein

Companion vein

Lymphatic vessels

Fibroblastnuclei

Smallmuscular

artery

Lymphaticvessels

Smoothmuscle fibers

Capillaries

Smallmuscular

artery

Collagenfibers

Smallermuscularartery (no IEL)

Figure 7-6. Companion arteries and veins of the small category are seen in these H&E-stained sections. Part A is from thesubmucosa of the colon (200×), and part B from the submucosa of the jejunum (240×). A, The vessels are of comparable caliberalthough the artery has a thicker wall and is somewhat rounder than its companion vein—a reminder that rules in biology arereplete with exceptions. The IEL of the artery is visible as a wavy red line with a few endothelial cell nuclei visible on the luminalsurface. The nuclei of smooth muscle cells of the tunica media are seen in both vessels. A number of lymphatic vessels are seennear the blood vessels; in a few of these, the endothelial cell nuclei can be identified. B, The paired vessels in this section areabout 20% smaller than those in part A (note the difference in magnification). In this case, the IEL of the artery is barely visible,but its presence is evident by the slight clear line under the endothelial cells and the wavy luminal border of the vessel. Themuch thinner wall and larger caliber lumen of the vein (allowing for the fact that the vein is probably obliquely sectioned), arealso evident. There are many lymphatic vessels in this section, some filled with slightly different amounts or concentrations oflymph fluid.

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