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TCD 20: Fatigue and Neck Swelling ? By Nazneen, Anna & MarwanSignupform→receiveemailwithfeedbackform→filloutfeedbackwithin24hrs→receiveslides+recording *Disclaimer* The content of this presentation was created by med students for med students. This session isn’t intended to replace any formal education provided by the uni of mani, so make sure to review all the cases on 1Med and read your ILOs and attend at least 40 hours/week of clinical experience ;)Admin Stuff - Youknowthedrill - Anyadminstuffpleaseemailscrubbed-up@outlook.comrather thanmessagingoneofuspersonally:)) - Stopcomplainingabouttheheatingomlenjoyitwe’relegitina costoflivingcrisisrntellmeurrichwithouttellingmeurrichLife rnSo what is this teaching exactly? Covers the main pathologies mentioned in each week’s TCD Progress Test, CCA/OSCE, DDx, top notch medics basically NOT HERE TO HOLD YOUR HAND THROUGH THE 1MED CASES SUCCINCT, HIGH YIELD, SHARP and ACCO IT’S نﺎﺳﺣإ SEASON PEOPLE !! No advice. Just pain. Morale is low. Discipline is a must. Contents ❏ PoopiepooppooplotsofpoopjustloadsofpoopeverywherepoopiepoopHaemostatic Physiology - R (wallahi this is genuinely a big big L)Intro to the Clotting Cascade TheclottingcascadeismadefromfactorsItoXIII Thesefactorsform3groups: 1. Intrinsicpathway 2. Extrinsicpathway 3. Commonpathway There’saseparatepathwaytodissolvetheclots Andwealsohavenatural/innateanti-coagulantstolimitcoagulationtothespecificareaof damageInnate/Natural anti-coagulation: ● Prostacyclin ○ InhibitsTXA2 ● AntithrombinIII ○ InhibitsIIa,IXa,Xa,XIa,XIIa ● Heparinsulphate ○ Co-factorthatenhancesAntithrombinIIIactivity ● ProteinC&S ○ DegradeVa,VIIIa ○ Activatedbythrombin ● tPa(tissueplasminogenactivator) ○ Activatesplasminogentoplasminwhichproceedstobreakdown(finesses)fibrin ThewayIrememberthe factorsfortheextrinsic pathway: FactorIII/Tissuefactor FactorVII III+VII=X Theextrinsicpathwaygoes intothecommonpathway (factorX) +vWfHow clots are dissolvedCoagulopathyT ests - R Be prepared for a truly haemorrhagic experience 11.30 Lab Test Flow Chart ● ProthrombintimePT(normal=approx9-13) ● ActivatedPartialThromboplastinTimeAPTT(normal=approx25-35) ● ThrombintimeTT(thoughnotoftendone) ● Fibrinogen ● Theclotting50/50test-Followuptesttoinvestigatecauseofunexplained prolongedAPTT/PT.Differentiatesbetweenpossibilityoffactordeficiencyor acquiredcoagulationinhibitors ● Why? ● [reminder:prolongedPTorAPTT=redotestwith50/50.Ifcorrects=factor deficiency.Iffails:afactorinhibitor]Prothrombin Time/ INR (12-13 seconds/0.8-1.2) PTsworkintensely1to5everyweek ● Theprothrombintime(PT)isameasureofthetimetakenforbloodtoclotvia the extrinsicandcommonpathways • You‘PlayTennisOUTSIDE’thereforePTisEXTRINSIC/COMMON). • Internationalnormalisedratio(INR) isastandardisedversionofthistest,commonly usedwithpatientsonanticoagulants. I(fibrin),II(thrombin),III(tissuefactor),V,VII,X(which Factors arerarelydeficientinisolation) Measureof overallclottingfactorsynthesisorconsumption Affectedby liverdisease,disseminatedintravascularcoagulation (DIC),vitaminKdeficiencyandwarfarinlevels. APTT (35-45 seconds) ApparentlyHenryVIIIdroveaVWafter9/11 ● Activatedpartialthromboplastintime(APTT) ● Timetakenforbloodtoclotviatheintrinsicpathway(‘PlayTableTennisINSIDE’thereforePTTis INTRINSIC). Factors factorsVIII(andvWF),IX,XIandXIIspecifically. Measureof overallclottingfactorsynthesisorconsumption Affectedby ○ Heparinoverdose ○ HaemophiliaA(VIII–X-linkedrecessive) ○ HaemophiliaB(IX–X-linkedrecessive) ○ HaemophiliaC(XI–autosomalrecessive) ○ vonWillebrand'sdisease(asvWFpairsup withfactorVIII) ○ canalsobeaffectedbyDIC,liverfailure, vitaminKdeficiency/warfarinleveland HEPARIN ● Note:anti-phospholipidsyndromecancausea highAPTTdespitebeingadisorderthatcauses clots,duetoitinactivatingthephospholipidused inAPTT. PT and APTT: Next steps SowedoaPTandit’sprolonged.What’sthemostcommonreasonforit beingdelayed? • Warfarin-apatientismorelikelytobeonadrugthanactuallyfactorVII deficient WedoanAPTTandit’sprolonged,whichdrugmightcausethis? • Heparin ThedysfunctionofwhichorganwillincreaseboththePTandAPPT? • Liver • Howcanwedistinguishbetweenfactordeficienciesor acquired/iatrogeniccoagulationinhibition? ○ CLOTTING50/50TEST-why/how? ○ [reminder:prolongedPTorAPTT=redotestwith50/50.Ifcorrects= factordeficiency.Iffails:afactorinhibitor] Bleeding Time (1-6 minutes for fingerprick) •Notusedanymoreduetobarbaricnature •Assuch,plateletspecificdisorderswillincreasetheoverallbleedingtime. Factors N/A Measureof overallplateletfunctionandlevels. Affectedby ○ Anti-platelettherapyoverdose ○ vonWillebrand’sdisease(vWFdeficiency –autosomaldominant) ○ Bernard-Souliersyndrome(GpIb deficiency) ○ Glanzmannthrombasthenia(GpIIb/IIIa deficiency) ○ TTP/ITP/HUS/DIC(lolkillmepls) ○ Thrombocytopaenia ○ Itoldyouhaematologyislegitillegal Thrombin Time (10-15 seconds) Incasesofaprolongedtime,thecauseiseithera syntheticissueor consumptionissue. Factors I(fibrin),II(thrombin),III(tissuefactor),V,VII,X (whicharerarelydeficientinisolation) Measureof howfastfibrinogenisconvertedtofibrinby thrombin Affectedby DIC,liverfailure,malnutrition,abnormal fibrinolysisandmanyotherconditionsPlatelet issues/Thrombophilia Haematology is not real btw, it's just a simulation 12.40Thrombophilia Progress test stuff! 3conditionsyoushouldbeawareof: - FactorVleiden:mutatedfactor5thatcan’tbebrokendownas normal(byproteinC)–mostcommonthrombophilia - Anti-thrombin3deficiency:thisisthemoleculethatheparinworks on.Thismoleculehelpsbreakdownthrombin.Withoutit,thepatient ismorelikelytoclot. ○ Innephroticsyndrome(whereproteinscanleakthroughthe becomehypercoagulable.losetheiranti-thrombin3moleculesand - Anti-phospholipidsyndrome:autoimmunehypercoagulabledisorderPlatelet Disorders - peak but needed ● Thrombocytopaenia→lowplateletcount ○ ↓↓Production-->BMfailure(aplasticanaemia)/infiltration (leukaemia/myeloma)/suppression(cytotoxicdrugs/radiotherapy). ○ ↑↑Destruction-->autoimmune(ITP)/non-immune(DIC/TTP/HUS) ○ Splenicsequestration(portalHTN/sickle-cell). Wewillcover:-ITHINKYOUUNDERSTANDWHYIDESPISEHAEMlol - ITP - TTP - HUS - APS - HHT - HSP - DICITP - Immune Thrombocytopenic Purpura - AntibodiesagainstglycoproteinIIb/IIIa/Ib-V-IXcomplex-->platelet destruction→SEVERETHROMBOCYTOPAENIA - Cause IsolatedThrombocytoPenia (ITPlol) - Types/management→ - Acute-->childrenpost-URTI/vaccination-->self-limiting~1-2weeks - Chronic-->adults-->relapsing-remitting-->prednisolone - Evan'ssyndrome-->ITP+AIHA - Ifrecurrentenough→SPLENECTOMYTTP - thrombotic thrombocytopenic purpura - ADAMTS-13deficiency(cleavesvWFmultimersintosmallerunits) - plateletaggregation-->smallvesselocclusion+thrombocytopenia - C-usinfection/pregnancy/drugs/malignancy/SLE/HIV - HAT-N - H:HaemolyticAnaemia - A:AKI - T:severeThrombocytopaenia - N:Neurostuff(Confusion/Seizures) DIC ● Innormalhomeostasis,coagulationandfibrinolysisarebalanced ● Coagulationcascade>thrombin,whichconvertsfibrinogentofibrinwhichformstheclot ● Fibrinolysisbreaksdownfibrinogenandfibrin,tobreakdowntheclot–thisisdonebyplasmin ● Thebreakdownofaclotresultsinpolypeptidescalledfibrindegradationproducts ● widespreadbleedingoccurs : lotsofclottingoccursand,becauseclottingfactorsgetusedup, ● Thecauseistissuefactor.Tissuefactorispresentonthesurfaceofmanycelltypesbutisnotnormallyin thecirculation.Itisexposedaftervasculardamageortraumawhereinmanyorgansaredamaged(TFis abundantinthelungsandbrainforexample). ● TFbindswithcoagulationfactorsandleadstoclots,henceanycauseforwidespreadTFexposureisbad!! ● Insepticpatientswherewesee widespreaddamageduetoinfectionforexample,thisexplainswhyDIC canoccur.Othercauses=traumaandmalignancy Rx: What are the typical findings on blood results? • Severely Low platelets • Prolonged APPT and PT FFP + platelets + heparin • Fibrin degradation products raised (Ddimer) • Schistocytes (microangiopathic haemolytic anaemia) Major Haemorrhage: - cryoprecipitateHSP - Henoch Schonlieneineien Purpura - IgA-mediatedsmallvesselvasculitis→nephriticsyndromeissue - 3-ishdaysPOST-URTI-mostlykids→SELF-LIMITING - Remember:siPAPImunyanyo - P:Polyarthritis - A:Abdopain - P:Pupuricrashonextensorsandbuttocks - Causedbythrombocytopaenialol - I:IgANephropathy(NephriticGN)HUS - Haemolytic Uraemic Syndrome - Primary-duetoatypicalcomplementdysregulation - S-cE.coli0157:H7-inkidsmostly-RxisIVfluidsandsupportivestuff Triad-HAT - HaemolyticAnaemia - AKI - Thrombocytopaenia - NoticehowsimilarthisistoTTP-Hxisv importantHHT - hereditary haemorrhagic telangiectasia - Raregeneticdisorderwithabnormalbloodvesselformation (telangiectasiaandarteriovenousmalformations[AVMs])whichcan causebleeding AkaasOsler-Weber-Rendusyndrome:ExtraTastyVealFondu - Epistaxis-->spontaneous/recurrentnosebleeds. - Telangiectasia-->multipleatcharacteristicsites(lips/oral cavity/fingers/nose). - Viscerallesions-->GItelangiectasia(with/without bleeding)/pulmonary/hepatic/cerebral/spinalAVMs. - Familyhistory-->afirst-degreerelativewithHHTAnti-Phospholipid Syndrome -Diagnosedbypresenceofantibodiessuchasanti-B2microglobulin,lupus anticoagulant,andanti-cardiolipin(mostimportantone)-2xtestsin12weeks -SymptomscanberememberedwiththemnemonicCLOT ○ C:clotsVTE/ATE ○ L:livedoreticularis-Capillaryclotting/mottlRx: No prior VTE: low aspirin ○ O:obstetriccomplications(miscarriages,stillbirths) ○ T:mildthrombocytopenia??? Hx of VTE : lifelong warfarin Pregnant? - LMWH + aspBLEEDING PROBLEMS - R Haematology is not real btw, it's just a simulation 12.40Haemophilia A -Whichclottingfactorisaffected? FactorVIII -Howisitinherited? X-linked but de novo mutations are common -Howdowediagnose? APTT and factor 8 levels (as well as hx) -Howdowetreat? Recombinant Factor VIII TDS -What‘stheroleofdesmopressin/DDAVP? In patients with mild deficiency, this will release factor 8 stores and raise levels through renal collecting duct resorption. -Cautionofusingdesmopressin? In some it can cause hypotension Haemophilia B (AKA?) Christmas disease -Whichclottingfactorisaffected? Factor IX -Howisitinherited? X-linked again (peak times for men alie) -Howdowediagnose? APTT and factor IX levels (as well as hx) -Howdowetreat? Give IV Recombinant Factor IX OD -ForbothhaemophiliaAandB,whatanti-fibrinolyticcanweuseto preserveanyclotsthatmayhaveformedinamajorbleed? Tranexamic acid Prophylaxis Hemophilia A/B Summary - Heam.A=factorVIII,3xweekly - Heam.B=factorIX,2xweekly (startat18m-3yrsorafter3rdjointbleed) Diagnosis - NormalPT Treatmentacutebleed - ProlongedAPTT-normalisingon50/50 - DeficiencyinfactorVIIIorIX - IVfactorVIIIorIXconcentrate - ONLYheam.A =Desmopressin - Supportivecare - Fibrinolyticagent=tranexamicacid Grading Totalprotein bleeding frequency site Mild 5-10% trauma rarely rarelyjoints Moderate 1-5% slightinjury 1xmonth lessoftenjoints Severe <1% spontaneous 1-2xweekly hemarthrosis/IMhemorrhageAcquired Haemophilia -Liverfailure -VitKdeficiency(II,VII,IX,X,C+S) -Autoimmune -DisseminatedIntravascularCoagulopathy(allclottingfactors rinsed) Whatwilltheseshowoncoagulationtesting?APTTPT,bleedingtime?Signs/Simptoms -spontaneoushaemorrhagewithoutanytrauma. -Paeds:intracranialhaemorrhage,haematomasandcordbleedingin neonates. -Spontaneousbleedingintojoints(haemoathrosis)andmusclesarea classicfeatureofseverehaemophilia andworthremembering. ○ Ifuntreatedthiscanleadtojointdamageanddeformity. - Bruising,oozingafterdentistappointment,haematuria -Abnormalbleedingcanoccurinotherareas: ○ Gums ○ Gastrointestinaltract ○ Urinarytractcausinghaematuria ○ Retroperitonealspace ○ Intracranial ○ Followingprocedures/surgeries Von Willebrand’s Disease - IsitmoreorlesscommonthanHaemophiliaA? More(mostcommonacc) - WhatisvWBf? EnablesfactorVIIItofunctionandattachmentofplateletstoendothelium - Symptoms Mucomembranous bleeds, Menorrhagia, Epistaxis - Howdowediagnose? Prolonged APTT, bleeding history, low Factor VIII levels vW activity : vW antigen 3 types = 1 mildest, type 3 very severe - 1: reduced amount of vWf - Howdowetreat? - 2: abnormal vWf - there is 2a (defected) and 2b (overactive) - 3: little or no vWf Minor bleed - TXA Type 1 → Desmopressin + TXA Type 2a → vW factor + desmopressin 2b → vW factor ONLY Type 3 → F8 concentrate and vW factorThrombocytopenia Lowplateletcount.Throwback:whichconditionhaveImentionedthat cancausethis? Anti-phospholipid syndrome Youwilllearnmoreaboutconditionsthatcanaffecttheplateletcount. Butonethingrelevanttothiscaseiswhentogiveplatelets.Anyone know? No need to give platelets unless their count is below 90 with an active bleed. Different trusts vary however on what point below 90 is indicative. WIth no bleeding, threshold might be below 10 DisseminatedIntravascularCoagulopathy Medications(sodiumvalproate,methotrexate,isotretinoin,antihistamines,PPIs,Alcohol) Immunethrombocytopenicpurpura Thromboticthrombocytopenicpurpura FORIMMUNECAUSESOF Heparininducedthrombocytopenia THROMBOCYTOPAENIA,WHYDON’TWE Haemolytic-uraemicsyndrome GIVEPLATELETS? LiverfailureCondition PT/INR APTT BT Plateletcount Notes VitaminKdeficiency/Warfarin ↑ ↑ – – DifferentINRrequiredinthemanagementofdifferentconditions,soahighvalue use maybenormalforthepatient(e.g.AF,valvereplacements,etc) HaemophiliaA/B/C – ↑ – – Symptomsof‘clotting’disorders:haemarthrosis,musclehaematomas,prolonged bleedingafterdentalsurgery vonWillebrand’sdisease – -/↑ ↑ – Symptomsof ‘platelet’disorders:petechiae,bruising,contactbleeding(e.g.gums), menorrhagia DIC ↑ ↑ ↑ ↓ Totalcoagulopathy,primarycausemustbetreated,giveplateletsandclotting factors ITP/TTP/HUS – – ↑ ↓ LackofPT/APTTderangementisagooddifferentiatorfromDIC,NEVERgive plateletstothesepatientsKey Points ForA Bleeding History PersonalHistory Family History Good idea to go head to toe: Basically just asking - Nose bleeds lasting > 30min? the same questions - Bleeding when brushing teeth common? but for their family. - Post-dental appointment bleeding? - Easy bruising? - Heavy periods? (sorry to ask Any early deaths in such a personal question the family? but...) - Miscarriages? - Any bleeds with surgery? Any known bleeding - Any frequent infections? disorders? - Any red flags? Weight, Fever, lumps - Hepatic cause? Ascites, jaundice, abdominal painTerminology and Precursor Knowledge 11.10TerminologyThe Spleen ● Thespleenhelpsfightbacteriaasitactsasareservoirforlymphocytes ● Inmanyconditionse.g.malignanciesandinfections,itcanenlarge (splenomegaly),presentingasamassintheleftupperquadrant. How do we differentiate it from an enlarged kidney? (OSCE golden nugget!) • Can't get above a spleen but you can get above a kidney • Dull to percussion • Moves down on inspiration Hypersplenism can lead to symptoms of anaemia, pancytopenia, infections, and bleeds as all the cells become stuck inside of it. May need to remove it if this occurs. A sign of a asplenism or hyposplenism is Howell Jolly bodies on a blood film.Lymph Nodes - as stated in your exam handbook  ●Painful=usuallybacterial ●Painless=viral,TB,orcancer ●Oval/rugbyshaped=good ●Footballshaped=bad ●Mobileandrubbery=good ●Ifhardandnon-mobile,thisissuggestiveof metastasis.  DescribingnecklumpsOSCETIP! SSS-SizeSiteShape CCC-ConsistencyContoursColour TTT-TemperatureTendernessTransilluminationNeck Lumps 11.15Probs best slide i’ll ever make icl but we move: Midline - Rises when sticking tongue out? → Thyroglossal Cyst - Rises when swallowing? → Thyroid Nodule/Goitre Anterior - Pulsatile? → Carotid Aneurysm triangle - Pulsatile + can be moved side-to-side but not up/down? → Carotid body tumour - teens + ~post-URTI --> cystic/oval/mobile? → Branchial cyst Posterior - presents <2 years old --> cystic + left-sided ? → Cystic hygroma triangle - halitosis + regurg + gurgles on palpation → Pharyngeal Pouch Anywhere - Punctum? → Sebaceous Cyst - smooth/mobile/painless → Lipoma - recent viral illness → Reactive Lymphadenopathy - painless + B symptoms? → LYMPHOMALymphomaLymphomas: Pathophysiology ● Alymphomaiswhenthenormallymphoidstructureisreplacedbymalignant proliferationoflymphocytes  ● Dependingonwhatthesecellslooklike,wecanclassifythem ● Hodgkin'slymphoma(HL)ischaracterizedby ____Reed-Sternberg Cells_______________? ● Non-Hodgkin'slymphoma(NHL)isfarmorecommon(80%oflymphomas) normallymphoidarchitecture,withoutthepresenceofRSCsanreplacethe ○ UsuallyfromBCellsorNKCells How are Reed-Sternberg cells described? •Bilobed, multinucleated lymph cells •"Owl's Eye appearance" Classifying Lymphomas The four ‘classical’ forms of HL (cHL) 1. HowmanytypesofHLarethere? account for around 95% of cases of HL. ● Nodular sclerosis: Most common subtype, accounts for around 70% of cHL. ● Mixed cellularity: Accounts for around 20% of cHL. 2. Whatarethesetypes? ● Lymphocyte-rich: Accounts for around 5% of cHL. Has the best prognosis. ● Lymphocyte-depleted: Rare, accounting for <1% of cHL. Has the the worst prognosis. 3. Whichtypeisseeninmen Nodular lymphocyte-predominant HL (NLPHL). andinthoseofblackethnicity? Very rare and has a distinct variant of the RS filmClassifying Lymphomas Youmayhaveheard Wecanclassifyalymphomausingwhichstagingsystem? ofAnnArborbut thatisold,likeZak. Lugano Staging - e.g. Someone with lymph nodes both sides of the diaphragm with no B symptoms would "A". be stage 3A. - Bulky refers to >10cm lesion - E means extra nodal involvementB Symptoms ● Fever Obviously it's not just lymphoma that causes B symptoms. What else does? ● Nightsweats ● Weightloss 1. TB! Important differential to consider 2. Other cancers ○ >10%in6ined, 3. Inflammatory and rheumatological conditions monthsHistory: Hodgkin's Lymphoma ●Therearetwopeaksofincidence:youngadultsandtheelderly ●RiskfactorsincludeEpstein-Barrvirus,HIV,andimmunosuppression ●Symptoms: ○ typicallyapainless,gradualrubberylump(usuallycervical), ○ aswellasBsymptoms(malaiseandfatigue) ○ Mediastinalmass→drycoughorSVCO ○ Hepatosplenomegalyand/orPruritis ●Onegoodquestiontothrowinis,doyougetpainwhenyou drink alcohol___?Diagnosis and investigations? Withalllymphomas,weneedasample.GOLDSTANDARDisexcisionbiopsy (notfine-needleaspirationorcore-biopsy).Wheretheaffectedlymphnodeis removedandanalysedhistologically. Spread to bone marrow can affect red Whataresomeotherusefulinvestigations? blood cell production Bedside Bloods Imaging • Lymph node exam • FBC (anaemia) • CXR (hilar • Abdo exam • Blood film lymphadenopathy) (hepatosplenomegaly) (Reed-Sternberg cells) • CT/PET TAP (thorax, • LDH (elevated) abdo, pelvis) [for • Uric Acid staging] • ESR • LFT LDH = lactate dehydrogenase converts • Marrow biopsy pyruvate to lactate. It's present in all • HIV, EBV, Hep B/C living cells so elevated amounts suggest a lot of cell turnover (destruction) What if, for whatever reason, a cHL patients needs a Blood/Platelet transfusion? Prognosis and Treatment To avoid transfusion-associated graft-versus-host disease, all cHL patients must receive irradiated red cells and platelets for life! ● PrognosisdependsonHLsubtype(don'tneedtoknowthem),age,ESR;butin general: ○ lowerstage+noBsymptoms=betterprognosis ● Treatmentisbothchemotherapyandradiotherapy(adjunct) ● TheagentsusedcanberememberedasABVD:adriazamycin,bleomycin,vinblastine, dacarbazine ○ Adriamycin/Doxorubicin-inhibitsDNAandRNAsynth.SE:cardiomyopathyandskinreactions ○ Bleomycin-inhibitsDNAsynth.SE:pulmonaryfibrosis,idiosyncraticreactions(lowBP,wheeze, confusion) ○ atonyastine-inhibitsmicrotubuleformationneededinmitosis.SE:peripheralneuropathyandurinary ○ Dacarbazine-methylationofguaninebases.SE:hepaticnecrosisandbonemarrowsuppression (pancytopenia) All you need to know Non-Hodgkin's Lymphoma about NHL to be honest ● AmalignantproliferationoflymphocytesthatdoesnotinvolveReed-Sternbergcells ● Themostcommonsymptomislymphadenopathy ● Mightnotinvolvejustnodes,e.g.thereareMALT(mucosaassociatedlymphoidtissue)lymphomas ● Riskfactorsinclude: ○ HIV(susceptibletoEBV),Immunosuppression,HPyloriplus1more!! ○ Whatcoulditbeeee??? ■ Coeliacdiseasecancauseanon-Hodgkin’sGutLymphoma ● LikeHLwecanusetheLuganoStaging ● Manytypes,wecanclassifythemashighgrade(aggressive)orindolent(non-aggressive) ● Wegenerallyseethathighgrade=easiertocure,butwithindolentitishardertotreat. ○ IsanyoneawareofaneyeconditionthathasasimilartreatmentresponsestyleasnHL? ■ Wet/DryAgeRelatedMacularDegeneration ● R-CHOPmostcommonregimentotreatmostcommonNHL→DLBCL(DiffuselargeBcell lymphoma)Indolent Lymphomas ● ExamplesincludefollicularlymphomasandMALT ● Asmentionedpreviously,thesearelikelytonotcausesymptoms  ● Theyrespondwelltotreatmentbutarehardtocompletelyeradicate  High Grade Lymphomas and is associated with HIV/EBVldren, • Examples include B cell lymphomas and Burkitt's lymphoma (c-myc proto-oncogene mutation) • Grows quickly (jaw, neck, abdomen → B0) and cause symptoms • Starry sky appearance on histology • Are more likely to be completely cured (chemo) than indolent lymphomasHodgkin’s vs Non-Hodgkin’s Summary ● Mostcommon? ○ NHL ● HL-RAAAA ○ Reed-Sternberg ○ Alcohol ○ Asymmetrical ○ Adjacent ○ AbruptBsymptomsHilar Lymphadenopathy Gimmesomecauses? ● Hodgkin'slymphoma(more commoninHLbutcan occurinotherlymphomas) ● Carcinoma ● Tuberculosis ● Sarcoidosis Sarcoidosis Sarcoidosisisachronicgranulomatousdisorderofunknown aetiology,commonlyaffectingthelungs,skin,andeyes. Itischaracterisedbyaccumulationoflymphocytesand macrophagesandtheformationofgranulomasinthelungsand otherorgans. Erythema nodosum/lupus pernio. Polyarthralgia. Symptoms? Swinging fever. SOB/dry cough/↓↓ weight CXR (bilateral lymphadenopathy - stage disease), ESR, serum ACE, Ca2+ Investigations? Biopsy diagnostic - looking for ? Treatment ? Steroids. Classical Immunosuppressants. Biologics. TransplantSVC Obstruction Thisisoneoftheoncologicalemergencies:thesuperiorvenacavaiseither compressedorblockedbyaclot/mediastinalmass.Thisstopsvenousreturn fromthehead,neck,andupperlimbs. Diagnosiscanbeclinicalandisbasedonwhatsymptoms? ● SOB Pemberton's test: ● Orthopnoea raising both arms ● Cyanosis ● Arm and face swelling causes cyanosis of the ● Distended head and neck veiface. Why? The clavicles ● Nonpulsatile raised JVP compress other veins, ● Red eyes exacerbating it. ● Pemberton's sign 8-16mg Dexamethasone bolus then CT for the cause. If immediate threat to life we can do an endovasc-SVC-stent with a balloon. Then use chemo/radiotherapy to reduce the mass.Tumour Lysis Syndrome ● AlotofthepreviousmalignanciesneedintensechemotherapyandradiationiftheCNSis involvedorforlocaldisease ● Fullbodyradiationmayalsobeusedinpreparationformarrowtransplants  •lymphoma, and myeloma, when chemotherapy is used to kill ● P-↑↑Phosphate the malignant cells we can see that huge amounts of cellu● U-↑↑Urea contents are released ● C-↓↓Calcium • 5 DAYS POST CHEMO → remember PUCKA ● K-↑↑Potassium • We prevent this by giving fluids and allopurinol ● AKI IV/rasburicase, and also making sure that chemotherapy is performed inside a hospital settingLeukaemia - Acute lymphoblastic leukaemia (ALL) - Acute myeloid leukaemia (AML) - Wallah I hate Haematology (WIHH) - Chronic lymphocytic leukaemia (CLL) - Chronic myeloid leukaemia (CML) HithinTerminologyAcute Lymphoblastic Leukaemia (ALL) Intro ● Themostcommonchildhoodmalignancy ● Lymphoidprogenitorcells(I.e.mostlyBcellsbutcanbeTcells)thatdonot mature(hencecalledblast cells)andkeepproliferating ● Peakincidenceisbetweenages0-4,aetiologyisunknownbuthasgenetic andenvironmental(virusexposure)roots. ● Theycanfillupthebonemarrow,blockingnormalhaematopoeticstemcell functionleadingtomarrowfailure,andinfiltratelymphoidtissuesaround thebodyAcute Lymphoblastic Leukaemia (ALL) Symptoms Bone Marrow Failure • Hepatosplenomegaly (60% of pt +ve) • Anaemia (no space for haematopoiesis) • Lymphadenopathy • Neutropenia (white cell count is high but • Orchidomegaly (testicular swelling) they don't function as normal) • Bone Pain • Thrombocytopenia • CNS symptoms: meningism and cranial nerve palsies, due to what? • Down’s syndrome children • Fatigue, SOB, Angina Leucostasis: high number of circulating • Recurrent infections white cells in the blood, causes • Petechiae, Nose/Gum bleeds, Bruising impairment of flow in small vessels. Therefore causing altered mental states and headaches from raised ICP, oedema, visual changes too. Can cause priapism in adults too.Acute Lymphoblastic Leukaemia (ALL) Diagnosis Diagnosis and investigations: • FBC, Coag, Ca2+, Urate, Renal, LFTs • Blood film and marrow aspiration with high blast cells • CXR and CT to look for disseminated lymphadenopathy • Lumbar puncture to look for CNS involvement • Cytogenetic analysis ( Karyotyping/ FISH) • TdT gene → Characteristic • TforCMLtmentischemo+radiotherapy,asforallleukaemiasexcept Acute Myeloid Leukaemia  ● Myeloidprogenitorcells(shouldbecomeredbloodcellsor plateletsorthenon-lymphoidwhitecells)thatdonotmature andproliferate. ● Poorlyunderstood,somecausesare:radiation,previous chemoandtoxicinsecticides ● MuchlikeALL,AMLcanleadtothesameinfections,easy bleeds,andanaemia. ● AsinALL,AMLhassimilarsignsandcanalsoinvadetissues ● Thetreatmentischemo+radiotherapy,asforallleukaemias exceptforCMLAML and ALL are quite similar, so how do we tell them apart? ● AMLcancausegumhypertrophyandviolaceous(violetcolouredlikethisslide hehe)skindeposits ● Furthermore, ALL affects children the vast majority of the time, whereas AML rarely affects children, but affects adults more so. ● It affects every other age group, median age is actually 70 so the elderly more so. Also linked to Trisomy 21.Blood Film In AML, a blood film will reveal Auer rods (needle shaped structures in the cell body). If you see auer rods in a question stem say alhamdulilah and smash the AML answer Chronic Myeloid Leukaemia ●Uncontrolledproliferationofmyeloidcells ●It'samyeloproliferativedisorder(proliferationofmyeloidstemcellsthatretaintheabilityto becomethedescendentcellse.g.platelets,RBCs,non-lymphocytewhitecells) ●Occursinthose40-60usually ●Symptoms: ○ Chronicandslowlydevelopingsymptomssuchasfatigue,fever,sweats,weightloss ○ Canhavegout ○ Bleedeasily ○ Splenomegaly(whichisoftenmassive,andverycharacteristic) ●Bloodfilmwillshowimmatureandmaturemyeloidcells,theratioofblaststobasophilstellsus progress. ●They'llhaveaveryhighWBC(oftenover100)withallcelltypeshigh(exceptlymphocytesof course)-ThisiscalledhighgranulocytesatdifferentstagesofdifferentiationCMLTreatment ● ThePhiladelphiaChromosome(aproductoftranslocation)ispresentin over80%ofcases ● Themutationcarriesabetterprognosisbecauseadrug,aTyrosineKinase Inhibitor, hasbeendevelopedspecificallyforit:imatinib ● Ifimatinibdoesnotwork,resorttointensive(AML)chemoregimen,ifnot thenstemcelltransplants ● CMLhas3phases:chronicphasewithfewBsymptoms,ifany;accelerated phasewithmoreBsymptomsandsplenomegaly;andthe blast transformationphasewhichcauseschangetoAMLorALL ○ Withouttreatment,blasttransformationCMLhasalife-expectancyofonlyafewmonths ● CMLismanagedlikeALLiswhenittransforms,andastemcelltransplant canbeusedtooChronic Lymphocytic Leukaemia  ● Thisisthemostcommonleukaemiaandisthemalignantproliferationof incompetentbutmaturedBcells ● ThereisawelldocumentedlinkbetweenTP53statusandprognosishere ● PatientsareoftenasymptomaticbutdependingontheseveritymayhaveThese infections,anaemia,malaise,weightlossandnightsweats.ry fragile cells that are damaged in ● Liketheothermalignancies,canleadtohepatosplenothe preparationss lymphadenopathy (thisisthehallmarkfeature,uptoprocess. AKA smear ● DeathhappensduetoinfectionortransformationtoRior basket cells. ● Usuallyaffectsthoseaged70orolder ● OnanFBCwe'dseeraisedWCCand,withmarrowinfiltration,lowHb, low platelets, andlowneutrophils.Whatwouldyouseeonafilm? CLLTreatment ● Thisisaslowlyprogressingdiseasebutsomepeopleneverprogress,andcanevengetabit better ● StagingisdoneviaBinetorRaisystems ● →ifallelsefailsweuseallogenicstemcelltransplantationstlychemo,TKIsorsteroid ● Wetreatwithdrugsifsymptomatic,lymphocytosisisworseningorautoimmune complicationsoccur ● Steroidscanhelpcounteractcomplicationslikeautoimmunehaemolysis(warmtype, investigatedviaindirectCoomb'stest)orITP ● Asstatedbefore,itcantransformintoanaggressivelymphomacalledRichter'slymphoma ● ThisisaNon-Hodgkin'slymphoma–thehighgrade Bcelllymphoma Summary (Because I don’t want to become a haematologist) Infections,Anaemia,Bleeding→Possibleleukaemiaduetoanaemia, thrombocytopaenia,leukopaenia Differentiatingfactorsbetweeneach: ALL→Children,down’ssyndrome,testicularswelling,TdTgene,blastcells AML→Auerrods,Children,gumswelling, adults CML→Elderly,Massivesplenomegaly,raisedWBCwithallraisedexceptfor lymphocytes,blast’stransformationtoAMLandALL,Philadelphia chromosome,Imatinibtotreat CLL→Elderly,symmetricallymphadenopathy,Smudge/smearcells,Richter’s transformationMultiple Myeloma 12.00 Symptoms of Other symptoms? Spinal Cord Compression Hypercalcaemia? bone pain, abdo pain, Multiple Myeloma Hyperviscosity (same a leucostasis) constipation, confusion, Recurrent infections polyuria ● Haematologicalmalignancyofmatureplasmacells(theseareactivatedBcells).It secretesexcessamountsofmonoclonalantibody/m-proteins-lightchain/IgG/IgA ● It'sthesecondmostcommonhaematologicalmalignancy  ● Thereare2premalignant:MGUSandSmouldering,almostallMMcomefromthese. ● Patientsaretypicallyaround70yearsoldatpresentationwithBsymptoms.Very hardtotreatifanything,overarchingthemeisthatitisnotcurable. ● AutologousBMTandhigh-doseChemoisallwehavefolkssadface</3 • C: hyperCalcaemia • C: osteoclast activity → Ca2+ → hypercalcaemia • R: the dysfunctional plasma cells release dysfunction Ig that • R: renal failure NOTE: damage the tubules → polyuria/dipsia Rx is mostly around • A: they invade the bone marrow and prevent RBC generation - • A: anaemia symptom Why? • B: osteoclast activity leads to lytic lesions which are painful and • B: bone pain management, the can cause fractures as the bone is weak drugs available are • B: thrombocytopenia • B: Bleeding the MPT regimen, • I: Neutropenia and dysfunctional antibodies • Infection they help treat this Investigation Results for MM Bence Jones monoclonal proteins (found in Rouleaux formations Raindrop skull urine via electrophoresis) (stacked RBCs) (bone lesions) Diagnosis requires: 1. >10% Monoclonal plasma cells in the bone marrow 2. Monoclonal proteins in the urine (BJ)/serum (IgA/IgG/light chains/β-2-microglobulin) on electrophoresis 3. Evidence of end-organ damage (e.g. anaemia, bone lesions, etc)Summary of Important Blood Film Results  Auer Rod = AML Smudge cell = CLL Howell-Jolly body = hypo/asplenism RS cell = HL Rouleaux formations = MMTysm :)