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Block 5 Revision Anatomy Anatomy of lymphatic drainage – 12/4/16 1. Describe the components of the lymphatic system and the functions of these components The lymphatic system is comprised of two semi-independent parts: the lymphatic vessels and lymph; and lymphatic organs and tissues. Lymphatic vessels play two key roles. Firstly, they drain excess interstitial fluid back into the blood, returning some lost plasma proteins in the process. Secondly, they transport dietary lipids from the intestine to the blood through specialised lymphatic capillaries called lacteals. Lymphatic organs and tissues play an important role in fighting infections through immune responses and are essential for both the adaptive and innate immune system. Lymphatic organs and tissues are classed into primary organs and tissues and secondary organs and tissues. Primary lymphatic organs and tissues are where stem cells divide and mature into B or T lymphocytes. It includes the red bone marrow (produces lymphocytes, B cell maturation) and the thymus (T cell maturation under the effects of thymosin). Secondary lymphatic organs and tissues are where most immune responses occur. They include lymph nodes (areas of concentrated lymphocytes in a special arrangement), spleen (similar to lymph node but large and filled with blood, plays a role in filtering and purifying the blood) and lymphatic nodules (which are congregations of lymphatic tissue, including the tonsils, Peyer’s patches and mucosa associated lymphoid tissue [MALT]). Primary lymphatic organs and tissues – B and T cell production and maturation Secondary lymphatic organs and tissues – sites of immune response Bone marrow • Lymphocyte production • B cell maturation Lymph nodes • Concentrated lymphocytes in special configuration Thymus • T cell maturation (thymosin) Spleen • Similar to lymph nodes, but filled with blood • Blood filtering and purification Lymphatic nodules • NOT encapsulated • Congregations of lymphatic tissue • Tonsils • Peyer’s patches • Mucosa associated lymphoid tissue (MALT) 2. Explain the formation of lymph and the mechanism of lymph transport In the systemic and pulmonary blood capillaries, the mean of interstitial and luminal oncotic and hydrostatic pressure can result in movement of blood (minus cells and large proteins) out of the capillaries and into the interstitium. The lymphatic

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Page 1: Block 5 Revision - StudentVIP

Block5Revision

AnatomyAnatomyoflymphaticdrainage–12/4/16

1. DescribethecomponentsofthelymphaticsystemandthefunctionsofthesecomponentsThelymphaticsystemiscomprisedoftwosemi-independentparts:thelymphaticvesselsandlymph;andlymphaticorgansandtissues.Lymphaticvesselsplaytwokeyroles.Firstly,theydrainexcessinterstitialfluidbackintotheblood,returningsomelostplasmaproteinsintheprocess.Secondly,theytransportdietarylipidsfromtheintestinetothebloodthroughspecialisedlymphaticcapillariescalledlacteals.Lymphaticorgansandtissuesplayanimportantroleinfightinginfectionsthroughimmuneresponsesandareessentialforboththeadaptiveandinnateimmunesystem.Lymphaticorgansandtissuesareclassedintoprimaryorgansandtissuesandsecondaryorgansandtissues.PrimarylymphaticorgansandtissuesarewherestemcellsdivideandmatureintoBorTlymphocytes.Itincludestheredbonemarrow(produceslymphocytes,Bcellmaturation)andthethymus(Tcellmaturationundertheeffectsofthymosin).Secondarylymphaticorgansandtissuesarewheremostimmuneresponsesoccur.Theyincludelymphnodes(areasofconcentratedlymphocytesinaspecialarrangement),spleen(similartolymphnodebutlargeandfilledwithblood,playsaroleinfilteringandpurifyingtheblood)andlymphaticnodules(whicharecongregationsoflymphatictissue,includingthetonsils,Peyer’spatchesandmucosaassociatedlymphoidtissue[MALT]).

Primarylymphaticorgansandtissues–BandTcellproductionandmaturation

Secondarylymphaticorgansandtissues–sitesofimmuneresponse

Bonemarrow• Lymphocyteproduction• Bcellmaturation

Lymphnodes• Concentratedlymphocytesin

specialconfigurationThymus

• Tcellmaturation(thymosin)Spleen

• Similartolymphnodes,butfilledwithblood

• Bloodfilteringandpurification Lymphaticnodules

• NOTencapsulated• Congregationsoflymphatic

tissue• Tonsils• Peyer’spatches• Mucosaassociatedlymphoid

tissue(MALT)

2. ExplaintheformationoflymphandthemechanismoflymphtransportInthesystemicandpulmonarybloodcapillaries,themeanofinterstitialandluminaloncoticandhydrostaticpressurecanresultinmovementofblood(minuscellsandlargeproteins)outofthecapillariesandintotheinterstitium.Thelymphatic

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capillariesarecloselyassociatedwiththeinterstitiumandexcessfluidflowsintothemtoeventuallyenterthelymphaticvessels.Thelymphaticvesselsofthepulmonarycirculationmeetatthelymphaticductwheretheyemptyintosystemicbloodcirculationatthesubclavianvein.Thelymphaticcapillariesplayakeyroleintheformationoflymph.Foundthroughoutthebodyexceptinavasculartissues(cartilage,epidermis,cornea),theyareporousandblind-endedandtheopeningsintothemarebetweentwotissuecells.Theseopeningshaveaone-wayvalvethatmeansthatfluidenteringthemfromtheinterstitiumcannotre-entertheinterstitium.

Onceinthelymphaticsystem,therearenopumpssospecialmechanismsforflowarerequired.Therearelotsofvalvesinthelymphaticvesselstoensurethatflowisonlyone-way.Theexitofthelymphofthelymphaticductisintoalow-pressurearea(thesubclavianvein–5mmHg)togiveapressuregradient.Therearealsospecialdrivingforcestokeeplymphmovingthroughthelymphaticcirculation.Thesmoothmuscleinthevesselwallassistsinpumpingthelymphthroughthevessels.Theskeletalmuscleneighbourassistsinmilkingoutlymph.Respirationcausesthethoraciccavitypressuretodecreaseandtheabdominalcavitypressuretoincrease,thuscreatingapressuregradienttodriveflowbackintothethoraciccavity(thatis,wherethethoracicductandthesubclavianveinarelocated).

3. Summarisethedrainageroutesofmajorlymphaticvesselsandlocationofmajor

clustersoflymphnodesThereare10principalgroupsoflymphnodes.Thefirsttwogroupsliealongsidekeymidlinestructures:thetrachea(trachealnodes,x1)andtheaorta/celiactrunk/SMA/IMA(deepnodes,x1).Thenextthreearewheretheupperlimbs(axillarynodesinaxilla,x2)andlowerlimbs(inguinalnodesalonginguinalligament,x2;femoralnodesalongfemoralvein,x2)attachtothetrunk.Thelasttwogroupsarewheretheheadandneckattachestothetrunk(cervicalnodesalongcourseofinternaljugularvein,x2;pericranialringalongbaseofhead,x2).

4. Compareandcontrastthelocation,histologicalstructureandfunctionsofprimary

andsecondarylymphaticorgans

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Seepracticalmanual

5. Relatetheanatomyofthelymphaticsystemwithclinicalscenarios:cancermetastasis,lymphoedemaHavingagoodunderstandingofthelymphaticsystemisimportantascertainareasofthebodydrainthroughcertainpathways.Therefore,thelymphaticspreadofcancercanbepredicted,ortraced.Threeexamplesaretheoesophagus,testesandscrotum,andtheupperlimbandbreast.

Partofoesophagus Drainsinto SitesofmetastasesUpper1/3 Deepcervicalnodes Middle1/3 Superiorandposterior

mediastinalnodes

Lower1/3 Leftgastricnodes->coeliacnodes

StomachDuodenumSpleenOmenta

Testicularandscrotalcancershavedifferentsurgicaltreatmentsduetothedifferencesintheirlymphaticdrainage.Thetestesdrainintothepara-artic/lumbarnodes,whereasthescrotumdrainsintothesuperficialinguinalnodes.Assuch,orchiectomy(removalofthetestes)shouldbedonethroughtheinguinalroute(NOTcuttingthroughthescrotumbutgoingthroughtheinguinalcanal)toavoidtumourspillageintotheinguinaldrainageroute(i.e.itavoidsthecancerpossiblyreachingthesuperficialinguinal).Differentareasofthebreastdrainintodifferentnodes(e.g.thelateralbreastdrainsintothepectorallymphnode).Itisimportanttocheckforlymphnodeenlargementwhendoingabreastexamasthisisoneofthemostcommonsitesofmetastasis.Infact,itisnecessaryforabreastcancertospreadtoatleastthesentinellymphnodeintheaxillabeforespreadinganywhereelsethroughthelymphaticroute.Post-mastectomylymphoedemaoccurswhentherehasbeentotalexcisionoftheaxillarylymphnodesthatoccurswithamastectomy.Becausethelymphaticdrainageiseffectivelycutoff,thereisnopressuregradientforthelymphtodrainsothefluidremainsintheinterstitium.Thiswillgiveaseverenon-pittingoedemaintheaffectedlimb.

PhysiologyHaematopoeisisanditsregulation–23/3/16

1. DefinehaematopoeisisHaematopoeisisistheprocessinwhichbloodcellsareformedinthebodyfromstemcells.

2. ContrasthaematopoieticstemcellsandprogenitorcellsHaematopoieticstemcells(HSCs)havedifferentpropertiestoprogenitorcells.

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Feature HSC ProgenitorcellHaematopoeiticcapacity(time)

Perpetual–canreconstituteandmaintainhaematopoeisisoveralongperiodoftime

Non-perpetual–cannotreconstituteandmainhaematopoesisoveralongperiodoftime

Proliferativecapacity Extensiveproliferativecapacity

Limitedproliferativecapacity

Self-renewal Canself-renew Limitedornoself-renewalcapacity

Pluripotency/unipotency Pluripotency–cangiverisetocellsofmanylineages(e.g.erythrocyte,granulocyte,Blymphocyte)

Multipotencyorunipotency–commitedtoalineage(e.g.lymphoid)

Activity Quiescent Activelycycling

3. DescribethesitesofhaemopoeisisbeforeandafterbirthBeforebirth Afterbirth4-5weeks:AortaGonadMesonephros(AGMregion)

Bonemarrow(pelvicbones,ribs,spine,skull,proximalpartofarmandlegbones)

4-6weeks:yolksac 6-22weeks:foetalliver 16weeks-9months:bonemarrow

4. Describeerythropoiesis,includingitsregulation,process,featuresandpurposeof

redbloodcells

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Erythropoeisisistheprocessthroughwhichredcellsaregeneratedinthebonemarrow.RedcellsareessentialforcarryingoxygentotissuesonHb.Theyareverysimplecells.Theydonothavenucleiandthereforecannotdooxidativemetabolism,relyinginsteadonglycolysisandthepentosephosphateshunt.Theyaresusceptibletofreeradicalsastheydonothavethepathwaysusuallypresenttoremovefreeradicals.TheythereforerelyonthePPPtogenerateantioxidantsandifapersonhasG6PDdeficiencytheredcellsaremorelikelytolyseunderconditionsofstress,resultinginhyperbilirubinaemiaandjaundice.Erythropoeisisisregulatedbyerythropoietin,whichisreleasedfromthekidneywhenlowO2tensionissensedbytheproximaltubule.EpoisinternalisedbytheEporeceptor(aJAKcytokinereceptor)intothemarrowprogenitorcellsanderythroidprecursorswhereithasanumberofeffects,includingthedifferentiationofHSCsintopronormoblasts.ItdoesthisbyALAsynthetaseformation,adenylylcyclaseactivationandtransferrinreceptorsynthesis.Epoisthenbrokendownwithinthereceptorsothatthereceptorcanberecycled.ErythropoesisisalsoregulatedbyIL-3whichpromotesthegrowthandreproductionofallthedifferenttypesofcommittedstemcells.OtherregulatoryfactorsincludeIGF-1,IL-6,andglucocorticoids,allowingincreaseinproductionofredbloodcellsduringtimesofacuteorchronicstress.Thiscanbedonebyincreasingtheactivityofthecommittedprogenitorcellsorthroughproductionofmoreprogenitorcells.Theprocessoferythropoiesisisshowninthediagrambelow.Basically,itgoesfromproerythroblasttonormoblasttoreticulocytetoerythrocyte(blast->cyte)andtakesabout7days.RBCsthensurviveinthecirculationforaround120days.Theyarethenbrokendownbymacrophagesinthespleenwhentheybecomesenescent.

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5. OutlinetheroleofJAK2inhaemopoeisisJAKisanintegralpartofacytokinereceptorthatsitsonthemembraneofmanycells,includingbonemarrowprogenitorcells.Whenthecytokine(e.g.Epo)bindstotheoutermembraneportionofthereceptor,thiscausesaconformationalchangeinthereceptorthatresultsinJAKphosphorylatingthecytoplasmicdomainofthereceptor.Whenthereceptorisphosphorylated,thisallowsthebindingofSTAT

Proerythroblast

Basophilicnormoblast

Polychromaticnormoblast

Orthochromaticnormoblast

Reticulocyte

Erythrocyte

Day115-20umBasophiliccytoplasm(polyribosomes)MitosisNucleuswithinnucleoliNoHb

Day214-17umMitosisBasophiliccytoplasmNucleolidisappearsDay310-15umPolychromasia(basophilicandeosinophilic)ChromatinlumpsHbappearsNucleuscondenses

Day47-10umPyknotic(shrunken)nucleusEosinophiliccytoplasmMitosesabsentExtrusionofnucleusHbismaximumDay5-77.3umEnterscirculationReticulumofbasophilicmaterialinthecytoplasm(clumpedribosomes,RER)

Day7-1207.2umHb

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proteintothecytoplasmicdomain.OnceSTATproteinisbound,JAKphosphorylatestheSTATprotein,allowingtheproteinstoassociateintoadimertoenterthenucleusandregulategenetranscription.‘

6. OutlinethestructureofthehaemoglobinmoleculeHaemoglobinhas2alphaglobinchainsand2betaglobinchains,eachofwhichcarries1unitofheme.Eachunitofhemecarriesanironatom.Thehaemoglobinmoleculecanthereforecarry4O2.ItundergoesconformationchangewhenO2associatesordisassociates,resultingintheO2saturationcurve.

7. Describegranulopoeisis,includingitsregulation,process,featuresandpurposeofthewhitebloodcellsGranulopoiesisistheprocessbywhichgranulocytesareformedfromthemyeloidstemcell.Granulocytesincludeneutrophils,monocytes,eosinophilsandbasophils.Thesecellshavedifferentfeatures(staindifferently,differentnuclei)androleswithintheimmunesystemincludingphagocytosisreleaseofgranulesandchromatinswhenneutrophilslysetoformanextracellularfibrilmatrixasaphysicalbarriertostoppathogenspread.Phagocytosiscanbedonebydirectlybindingthebacterium,bindingthebacterium+C3bontheC3breceptor,bindingofthebacterium+antibody+C3bontotheirC3breceptorandFcreceptor.Theyreachsitesofinflammation,tissuedamageandimmunereactionsbytheprocessofchemotaxis,wheretheyfollowsignalssuchasC5atocrosstheendotheliumandbasementmembraneofthecapillarybloodvesseltoreachtissue.GranulopoeisisisregulatedbyGCSF(granulocytecolonystimulatingfactor)whichisproducedbytheendothelium,macrophagesandotherimmunecellsfromageneonchromosome17.ItbindstoGCSFreceptorsonmyeloidprogenitorswhereitistheninternalised.GCSFisusedinthebasalproductionofgranulocytes.AnotherimportantregulatorisIL6whichissecretedbymonocytesandfibroblastsduringacutestress(e.g.infection).IL6isusedintheemergencyproductionofgranulocytes.Thefollowingdiagramdescribesthestagesofgranulopoeisis.Theprocesstakesover14days.

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Myeloblast

Promyelocyte

Myelocyte

Metamyelocyte

Bandcell

Granulocyte

CommittedcellDiameter14-18nmOvalnucleuswithmultiplenucleoliNogranules

18-30umOvalnucleusCondensedchromatinPurple-stainingnonspecificazurophilicgranules

12-15umPresenceofsmallerspecificorsecondarygranulesCytoplasmbecomeslessbasophilic

12-15umNomoregranuleproductionReducedcellsizeNucleusbecomesflattenedChromatincondensation

Nucleushorse-shoeshapedCellsizedecreases

NucleussegmentedintolobesCellsizedecreasesEntersthebloodstream


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