HISTOLOGY OF THE CARDIOVASCULAR SYSTEM Peter B. Baker, M.D. e-mail Peter.Baker!"ati#"$i%e&'il%re"(.

#r) Reference source for eLearning, Histology-Cardiac, Week 1, April 1, 2014 Page References - Leslie P !artner and "a#es L Hiatt Color $e%t&ook of Histology, 'rd (dition, W) *aunders, 200+ I. HEART A. Atrial a"% *e"tri&+lar a"at#m, 1 Rig,t atriu# - recei.es syste#ic .enous return t,roug, superior and inferior .ena ca.a, coronary sinus/ fossa o.alis 0fora#en o.ale1, atrial appendage 2 Rig,t .entricle - t,in 2all 00 ' c# t,ick1, coarse apical tra&eculations, supra.entricular crest separates inflo2 fro# outflo2 tract, #e#&ranous .entricular septu# &e,ind t,e 3unction of t,e septal and anterior tricuspid .al.e leaflets, pro#inent #uscle &undles include #oderator &and and septo#arginal tra&eculation ' Left atriu# - recei.es pul#onary .enous return/ flap .al.e of t,e fora#en o.ale, tu&ular atrial appendage 4 Left .entricle - t,ick 2all 01 - 1 4 c#1, anterior #itral .al.e leaflet separates t,e inflo2 and outflo2 tracts B. M,#&ar%i+m -re.er t# // 012-013, 034-035 a"% 613-6157 $,ere are no 2ell-defined layers in t,e .entricular #yocardiu# 5uscle &undles are co#posed of parallel #yocytes 5yocytes are also called cardio#yocytes and #uscle fi&ers $,e #yocardiu# consists of #yocytes, collagen, &lood .essels, adipose tissue 0#ore in t,e rig,t .entricle t,an t,e left .entricle1 and ner.es (ac, #yocyte is surrounded &y &ase#ent #e#&rane co#posed of collagen and la#inin $,e cell #e#&rane is called t,e sarcole##a 5yocytes ,a.e one or t2o centrally located nuclei and t,e cytoplas# ,as a striated appearance due to t,e contractile proteins 0descri&ed &elo21 Alt,oug, #yocytes appear to &e arranged end-to-end, t,ere is considera&le &ranc,ing 2,ic, produces a co#ple% arrange#ent of interconnection Cardiac #yocytes are appro%i#ately 64 to 100 #icrons in lengt, and 14 to 16 #icrons in dia#eter 7ltrastructure of t,e 5yocardiu# Cardiac #yocytes and skeletal #uscle cells s,are #any ultrastructural features 1 Contractile structures $,e contractile proteins are organi8ed into 2ell-defined, parallel units called #yofi&rils (ac, #yofi&ril contains a nu#&er of proteins including t,in fila#ents 0actin1 and t,ick fila#ents 0#yosin1 $,ese t2o fila#ents,

called #yofila#ents, are arranged in ,ig,ly organi8ed repetiti.e units called sarco#eres Refer to figures 6-4 on page 191 and 6-4 on page 192 as 2ell as 5usculoskeletal )lock and &e sure you can identify t,e : disk 0&and1, ; &and, A &and, H &and and 5 line <ote t,at eac, #yosin fila#ent is surrounded &y 9 actin fila#ents 2,ere t,e t2o fila#ents o.erlap $,ere are a fe2 i#portant points a&out t,e structure and co#position of t,e #yofi&rils a =ne sarco#ere is t,e structure &et2een t2o consecuti.e : disks & $,e A &and is t,e lengt, of t,e #yosin fila#ents and t,e actin fila#ents run fro# t,e : disk to t,e edge of t,e H &and c $,e t,in fila#ents, in addition to actin, contain troponin ;, C and $ as 2ell as tropo#yosin <e&ulin e%tends along t,e lengt, of actin and acts as a te#plate to regulate t,e t,in fila#ent lengt, Alp,a actinin is a : disk protein t,at &inds t,e t,in fila#ents in parallel arrays d $itin is a protein attac,ed to t,e t,ick fila#ents and e%tends fro# t,e : disk to t,e 5 line $itin #aintains t,e central position of t,e t,ick fila#ents in t,e sarco#ere e Creatine kinase 2,ic, cataly8es t,e for#ation of A$P fro# A>P, is a #a3or co#ponent of t,e H &and f >etails of t,e #ec,anis# in.ol.ed in #uscle contraction are &eyond t,e scope of t,is lecture Calciu# &inding to troponin C acti.ates a confor#ational c,ange 2,ic, causes actin fila#ents to slide along #yosin fila#ents $,e sliding #o.e#ent is dependent on A$P g >uring contraction t,e A &and 2idt, does not c,ange $,e ; &and 2idt, is greater during rela%ation and narro2er during contraction 2 $rans.erse 0$1 $u&ules $ tu&ules are in.aginations of t,e cell #e#&rane 0sarcole##a1 into t,e cytoplas# along t,e : disks (ac, $ tu&ule is in close contact 2it, a sarcoplas#ic reticulu# tu&ule $,e site of contact is called a dyad <ote t,at in skeletal #uscle t,e $ tu&ules are in close contact 2it, t2o sarcoplas#ic reticulu# tu&ules, called a triad W,en t,e action potential reac,es a #yocardial cell, calciu# initially enters t,e cytoplas# t,roug, calciu# c,annels in t,e sarcole##a and $ tu&ules $,is triggers a greater release of calciu# fro# t,e sarcoplas#ic reticulu# tu&ules ' *arcoplas#ic reticulu# $,is speciali8ed s#oot, endoplas#ic reticulu# stores calciu# during rela%ation and releases calciu# into t,e cytoplas# to induce contraction 4 =t,er cytoplas#ic ele#ents 5itoc,ondria, glycogen, inter#ediate fila#ents 0des#in and .i#entin1, lipid and lipofuscin 0found ad3acent to t,e nucleus and increases 2it, increasing age1 4 ;ntercalated disks

*peciali8ed 3unctional co#ple%es 0intercalated disks1 3oin #yocytes endto-end and side-to side $,ey ,a.e a step2ise configuration *eg#ents perpendicular to t,e long a%is 3oin #yocytes end-to-end and ,a.e des#oso#es 0pro.iding #ec,anical attac,#ent1 and fasciae ad,erentes 0t,e attac,#ent sites for actin fila#ents in t,e last sarco#ere1 $,e seg#ents of intercalated disks oriented parallel to t,e #yocytes contain gap 3unctions $,ese 3unctions are sites of ionic co##unication &et2een cells and pro.ide for sync,ronous #uscle contraction 9 Atrial cytoplas#ic granules Atrial #yocytes, predo#inantly in atrial appendages, ,a.e cytoplas#ic dense granules 2,ic, contain atrial natriuretic peptide 0A<P1 W,en t,e atria are distended t,is polypeptide is released A<P causes diuresis 0increased urine output1 &y increasing glo#erular filtration rate in t,e kidneys, increasing sodiu# and 2ater e%cretion and antagoni8ing t,e action of angiotensin ;; and renin + >ifferences &et2een skeletal and cardiac #uscle Cardiac *keletal Central, single nucleus Perip,eral, #ultiple nuclei $ tu&ules at le.el of : disks $ tu&ules at A-; 3unction ;ntercalated disks <o intercalated disks $ tu&ule - *R 3unction, dyad $ tu&ule - *R 3unction, triad Cytoplas#ic granules 2it, A<P 0atria1 <o granules ?e2er *R tu&ules 5ore #itoc,ondria 2it, #ore cristae C. E"%#&ar%i+m -// 613-6187 $,is is t,e inner lining of all t,e ,eart c,a#&ers and consists of an endot,elial lining and su&endot,elial collagen and elastic fi&ers D. Vi(&eral /eri&ar%i+m -/ 6157 $,e surface of t,e ,eart is co.ered &y a si#ple layer of #esot,elial cells 2it, a t,in underlying layer of collagen E. E/i&ar%i+m -/ 6157 $,is is t,e connecti.e tissue &et2een t,e .isceral pericardiu# and t,e #yocardiu# $,e epicardiu# contains collagen, adipose tissue, &lood .essels and ner.es F. A"at#m, #. t'e &ar%ia& *al*e( 1 Arterial .al.es 0pul#onary and aortic1 - $,ree se#ilunar leaflets, ad3acent leaflets are co#pletely separate fro# eac, ot,er at t,e co##issures *inus of @alsal.a is a pocket in t,e root of t,e aorta or pul#onary artery &e,ind eac, leaflet

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2 $ricuspid .al.e - Anterior, posterior and septal leaflets are anc,ored to papillary #uscles and t,e .entricular 2all &y c,ordae tendineae $,e leaflets attac, to t,e 2all along a circular annulus $,ere is no fi&rous continuity &et2een t,e tricuspid and pul#onary .al.es ' 5itral .al.e - Anterior and posterior leaflets are anc,ored to anterior and posterior papillary #uscles &y c,ordae tendineae and t,e leaflets are attac,ed to t,e 2all along a circular annulus ?e2 c,ordae also attac, to t,e .entricular 2allA ,o2e.er, none attac, to t,e .entricular septu# $,e co##issures are arranged 2it, one posterior and #edial and t,e second anterior and lateral $,ere is fi&rous continuity &et2een t,e anterior leaflet and t,e aortic .al.e $,e anterior leaflet di.ides t,e inflo2 fro# t,e outflo2 tract in t,e left .entricle G. Car%ia& *al*e( $,e tricuspid and #itral .al.es ,a.e 4 identifia&le ,istologic layers $,ey are listed in order fro# t,e atrial surface to t,e .entricular surface 1 Atrialis - a t,in layer of dense collagen 2 *pongiosa - a t,in, irregular layer of loose collagen 2it, proteoglycans ' ?i&rosa - dense collagen for#ing #ost of t,e cross-sectional area of t,e leaflet and pro.iding tensile strengt, 4 @entricularis - a t,in, poorly de#arcated layer of dense collagen 4 C,ordae tendineae ,a.e a dense central core of collagen and a perip,eral t,in layer of elastic fi&ers $,e pul#onary and aortic .al.es ,a.e si#ilar layers as descri&ed a&o.e H. C#"%+&ti#" (,(tem -/ 6187 $,e speciali8ed conduction syste# consists of t,e sinoatrial 0*A1 node, atrio.entricular 0A@1 node, &undle of His and &undle &ranc,es co#posed of Purkin3e cells $,e #uscle cells of t,e *A node, A@ node and &undle of His are s#aller and contain fe2er #yofi&rils co#pared 2it, t,e contractile #yocytes $,e Purkin3e cells of t,e &undle &ranc,es are larger &ut contain fe2er #yofi&rils and #ore glycogen t,an t,e contractile #yocytes 1 *A node is located in t,e su&epicardial area at t,e 3unction of t,e rig,t atrial appendage 2it, t,e superior .ena ca.a $,ere are no #orp,ologically recogni8a&le speciali8ed conduction &undles &et2een t,e *A node and t,e A@ node 2 A@ node is located in a su&endocardial location 3ust a&o.e t,e septal leaflet of t,e tricuspid .al.e $,is node gi.es rise to a &undle 2,ic, courses anteriorly t,roug, t,e central fi&rous &ody and is called t,e &undle of His $,e distal aspect of t,e His &undle gi.es rise to left and rig,t &undle &ranc,es, 2,ic, course along t,e su&endocardial area of t,e inter.entricular septu# 0rig,t and left sides1 until #erging 2it, contractile

#yocardiu# II. VASCULAR -CIRCULATORY7 SYSTEM -// 640 - 6307 A. Arterie( Arteries ,a.e ' clearly identifia&le layers or tunics/ inti#a 0inner layer1, #edia and ad.entitia 0outer layer1 ;n all arteries, t,e inti#a is co#posed of an endot,elial lining and su&endot,elial collagen Larger #uscular arteries and elastic arteries #ay ,a.e a fe2 s#oot, #uscle cells and #acrop,ages in t,e inti#a $,e ad.entitia is co#posed of collagen and a fe2 elastic fi&ers $,e elastic arteries ,a.e s#all .essels in t,e ad.entitia and outer #edia called t,e .asa .asoru# $,ese .essels pro.ide o%ygen and nutrients to t,e outer layers of t,e arteries $,e inner layers of large arteries and t,e entire 2all of s#aller arteries recei.e o%ygen and nutrients directly fro# t,e .essel lu#en $,e structure of t,e #edia .aries in different arteries as descri&ed &elo2 1 (lastic arteries $,ese arteries do not contract &ut a&sor& t,e systolic pulse 2a.e &y distending and t,ey #aintain diastolic pressure &y elastic recoil (lastic arteries ,a.e a poorly defined internal elastic layer &et2een t,e inti#a and #edia $,e #edia ,as concentric elastic la#ellae 2it, interspersed s#oot, #uscle cells, collagen and proteoglycans $,ere is no e%ternal elastic layer $,e largest arteries 0aorta, pul#onary artery, &rac,iocep,alic artery, co##on carotid arteries, su&cla.ian arteries and co##on iliac arteries1 are elastic arteries 2 5uscular arteries $,ere is a gradual transition fro# elastic arteries to #uscular arteries 5uscular arteries range fro# fairly large cali&er .essels to s#all .essels #easuring only 140 # in dia#eter 5uscular arteries can contract and ,a.e a role in controlling &lood distri&ution to .arious organs $,e inti#a and #edia are separated &y a pro#inent internal elastic layer $,e #edia is co#posed of spirally arranged s#oot, #uscle cells, fe2 elastic fi&ers and sparse collagen $,e #edia and ad.entitia are separated &y an e%ternal elastic layer ' Arterioles Arterioles regulate &lood flo2 to different capillary &eds &y dilating and constricting Precapillary sp,incters are located &et2een arterioles and capillaries and control &lood flo2 into capillary &eds Partial contraction 0or tone1 of arteriole s#oot, #uscle can ,elp regulate &lood flo2 and generali8ed increase or decrease in tone can increase or decrease &lood pressure Arterioles are 20 to 1'0 # in dia#eter $,ey ,a.e a t,in internal elastic layer and no e%ternal elastic layer $,e #edia is for#ed &y one to se.eral layers of s#oot, #uscle cells and t,e ad.entitia is t,in 7nder certain conditions 0i e ,ypertension, dia&etes #ellitus1 plas#a proteins

accu#ulate in t,e #edia called ,yalini8ation or ,yaline arteriolosclerosis ;n so#e tissues, arterioles gi.e rise to #etarterioles 2,ic, ,a.e a discontinuous s#oot, #uscle #edia B. Ca/illarie( !as and nutrient e%c,ange occurs at t,e le.el of t,e capillaries $,ese .essels ,a.e .ery t,in 2alls co#posed of endot,elial cells surrounded &y a &ase#ent #e#&rane Pericytes are located along t,e outside of t,e capillaries $,e dia#eter is 4-10 # *ince red &lood cells are +# in dia#eter, t,ey #ust defor# to pass t,roug, t,e s#allest capillaries $,e ter# #icro.asculature refers to ter#inal arterioles or #etarterioles, capillaries and post capillary .enules *lig,tly larger capillaries 0preferential or t,oroug,fare c,annels1 ,a.e continuous flo2 and s#aller 0true1 capillaries ,a.e inter#ittent flo2 regulated &y precapillary sp,incters Wit, decreased o%ygenBnutrient reCuire#ents t,e precapillary sp,incters close and &lood is routed t,roug, t,oroug,fare c,annels *o#e .ascular &eds ,a.e arterio.enous connections 0t,roug, c,annels1 connecting ter#inal arterioles 2it, postcapillary .enules and &ypassing t,e capillary &ed $,ere are t,ree types of capillaries &ased on t,e endot,elial #orp,ology 1 Continuous capillary $,e endot,elial cells for# a co#plete, continuous lining $ig,t 3unctions are for#ed at points of cell to cell contact $,e &ase#ent #e#&rane is also continuous (%c,ange occurs &y diffusion 0of gases1 and t,roug, pinocytotic .esicles 0or ca.eolae1 )idirectional transport of su&stances is called transcytosis $,ese capillaries are found in #uscle, &rain, &one, lung and ot,er tissues 2 ?enestrated capillary $,e endot,elial cells ,a.e pores or fenestrae 0,oles t,roug, t,e cell1 2,ic, are 10 to 100 n# in dia#eter *o#e fenestrae are co#pletely open and so#e ,a.e a t,in diap,rag# $,e &ase#ent #e#&rane is continuous and for#s an i#portant diffusion &arrier o.er t,e fenestrae $,ese capillaries are present in sites of ,ig,er fluid transport suc, as glo#eruli and intestine ' >iscontinuous 0sinusoidal1 capillary $,ere are gaps &et2een endot,elial cells and larger fenestrae t,roug, indi.idual cells $,e &ase#ent #e#&rane is discontinuous $,ese capillaries are found in sinusoidal tissues 2,ere free e%c,ange &et2een &lood and t,e parenc,y#a is needed suc, as li.er and spleen C. Vei"( Postcapillary .enules are structurally si#ilar to capillaries $,ey ,a.e a 2ider lu#en and are t,e preferred sites for #igration of leukocytes into tissue 0called diapedesis1 5uscular .enules connect t,e postcapillary .enules 2it, larger .eins @eins ,a.e t,inner 2alls and are #ore distensi&le co#pared 2it, arteries of t,e

sa#e si8e A s#all increase in lu#inal ,ydrostatic pressure in .eins #ay significantly increase &lood .olu#e $,is can lead to pooling, congestion and stasis @eins ,a.e layers si#ilar to arteriesA ,o2e.er, distinction &et2een layers is less clear $,ere is no internal or e%ternal elastic la#ina $,e #edia is t,inner and t,e s#oot, #uscle cells ,a.e irregular 0roug,ly circular1 orientation ;n so#e .eins t,ere is a single #ediaBad.entitial layer @enous .al.es are pro3ections of inti#a $,e .al.es ,a.e a t,in central core of collagen and elastic fi&ers co.ered &y endot,eliu# $,e .al.es pre.ent retrograde &lood flo2 D. L,m/'ati& *e((el( -/ 632-6307 $,e ly#p,atic syste# &egins as &lind-end capillaries $,ese .essels ,a.e an endot,elial lining lacking tig,t 3unctions and lacking a co#plete &ase#ent #e#&rane At so#e points t,e endot,elial cells are directly anc,ored to ad3acent connecti.e tissue &y fila#ents $issue fluid along 2it, al&u#in and large #olecules enter t,e capillaries $,e capillaries drain into larger ly#p,atic .essels, e.entually leading to t,e t,oracic duct or rig,t ly#p,atic duct Larger ly#p,atic .essels ,a.e t,ree layers in t,e 2all, si#ilar to s#all .eins @al.es are present as seen in .eins Ly#p, nodes are located along t,e pat,2ay of ly#p,atic .essels ?luid is pus,ed t,roug, ly#p,atics &y intrinsic #uscular contraction 0triggered 2,en a seg#ent &eco#es distended1, contraction of ad3acent skeletal #uscle, arterial pulsation and co#pression fro# outside t,e &ody <o ly#p,atic .essels are present in cartilage, &one, central ner.ous syste#, &one #arro2 or surface epit,eliu# E. S/e&iali9e% &a/illar, :e%( 5ost capillary &eds are &et2een arterioles and .enules Ho2e.er, t,ere are e%ceptions $,e renal glo#erulus is an arterial portal syste# )lood enters t,e glo#erular capillaries t,roug, an afferent arteriole and e%its .ia an efferent arteriole $,e efferent arteriole t,en gi.es rise to anot,er capillary &ed, t,e .asa recta, 2,ic, surrounds renal tu&ules 0loops of Henle1 Capillaries in t,e li.er represent a portal .enous syste# ;ntestinal tract capillaries drain into t,e portal .ein $,e portal .ein leads to sinusoidal capillaries in t,e li.er 2,ic, t,en drain into ,epatic .eins A si#ilar portal .enous syste# e%ists in t,e pituitary Capillaries of t,e ,ypot,ala#us drain .ia .eins in t,e pituitary stock 2,ic, t,en gi.e rise to a capillary &ed in t,e anterior pituitary